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OBJECTIVES: The use of continuous glucose monitors (CGM) provides a more in-depth characterization of glycemic variation in response to environmental stimuli, but concerns about CGM reliability for categorizing glycemic responses to foods and meals exist. We sought to evaluate the concordance and reliability of two simultaneously worn CGM devices on postprandial glycemic responses. METHODS: We examined the correlation and coefficient of variation of the 2h glucose incremental area under the curve (iAUC) for 21,527 standardized and ad libitum meals consumed by 368 healthy participants from the PREDICT-1 Study. Included participants were simultaneously monitored with either two Abbott Freestyle Libre Pro devices (n = 339, same device group) or the combination of Abbott Freestyle Libre Pro and Dexcom G6 devices (n = 29, inter device group). Within-subject 2 h iAUC glucose meal rankings for paired CGM devices were assessed using the Kendal-tau measure for ranking concordance. RESULTS: The correlation coefficient of the 2 h glucose iAUC for paired CGM devices was 0.97 (95% CI, 0.96 to 0.97) for same device comparisons and 0.78 (0.76 to 0.80) for inter device comparisons. The coefficient of variation of the 2 h glucose iAUC for standardized meals was 5.1% (interquartile range, 2.2 to 10.1) for same device comparisons and 15.1% (5.9 to 31.2) for inter device comparisons. Similar results were observed for ad libitum meals with same and inter device coefficients of variation of 8.9% (3.3 to 21.3) and 24.2% (10.2 to 53.1%), respectively. Meal rankings for the 2 h glucose iAUC were concordant between paired CGM devices, with a mean Kendall rank correlation coefficient of 0.86 (sd = 0.07) for same device comparisons and 0.63 (sd = 0.011) for inter device comparisons. CONCLUSIONS: These data provide evidence for repeatability and concordance for ranking of glycemic responses, and suggest that factors other than CGM sensors mostly drive within-subject meal categorization. Our findings are critical for identifying sources of variability in glycemic responses for the eventual implementation of precision nutrition. FUNDING SOURCES: Zoe Global, UK Government Department of Health and Social Care, Wellcome Trust. National Institutes of Health.

OBJECTIVES: Approximately 30% of adults ≥ 50 years of age suffer from poor sleep quality and the prevalence of sleep disruption is notably higher in postmenopausal women, with 35 to 60% reporting significant sleep disruption. Sleep deprivation and low sleep quality are associated with increased energy intake, insulin resistance, elevated glucose, and mood disturbances (e.g., stress, cortisol, and depression). The objective of this study was to determine if the effect of protein and/or omega-3 fatty acid (O3FA) supplementation improves mood and sleep in postmenopausal women. METHODS: Thirty-nine postmenopausal women (age: 61.3 ± 8.7 years; BMI: 27.6 ± 6.6 kg/m(2)) were randomly allocated to one of 5 groups: 1) control (CON; no intervention free-living; n = 6), 2) whey protein isolate (PRO; 25 g/d; n = 7), 3) O3FA (DHA/EPA; 4.3 g/d; n = 10), 4) PRO + placebo soybean oil (PRO + PLA; 4.1 g/d; n = 7), or 5) PRO + O3FA (n = 9). Sleep and mood states were assessed at 0, 4, 8, 12, and 16 weeks, except objective sleep, which was assessed at 0, 8, and 16 weeks. Sleep was measured using the Pittsburgh Sleep quality Index (PSQI) and wrist actigraphy, mood was measured using the Profile of Mood States (POMS), and markers of sleep and mood, orexin, BDNF, and cortisol, were measured using commercially available kits. RESULTS: A significant time effect (P

OBJECTIVES: Elevated circulating branched-chain amino acids (BCAAs) during insulin resistance are strong predictors of type 2 diabetes mellitus onset. Defects in BCAA degradation are evident in several tissues during insulin resistance and non-alcoholic fatty liver disease (NAFLD). Furthermore, alterations in BCAA metabolism are associated with changes in several aspects lipid metabolism, including lipogenesis, ketogenesis and mitochondrial TCA cycle activity. Considering the crosstalk between BCAAs and lipid metabolism, we hypothesized that chronic supplementation of BCAAs will modulate hepatic insulin resistance and mitochondrial lipid oxidation during NAFLD. METHODS: Mice (C57BL/6N) were reared on either a low-fat (LF; 10% fat kcal), high-fat (HF; 60% fat kcal or high-fat diet supplemented with BCAA (HFBA; 150% BCAA) for 24 weeks. Metabolic profiling was conducted under fed or overnight fasted (14–16 hrs) conditions. A subset of overnight fasted mice from the HF and HFBA groups were subjected to hyperinsulinemic euglycemic clamps, following implantation of jugular vein catheters. RESULTS: Feeding HF and HFBA diets resulted in NAFLD. Circulating BCAAs were higher in ‘fed’ mice consuming HFBA diet (e.g., Valine, µM ± SEM; 311 ± 38 in HF, 432 ± 34 in HFBA, P ≤ 0.05). Overnight fasting significantly reduced BCAA levels in all groups, but the fasting levels of BCAAs remained similar between groups. Fed-to-fasted fold changes in blood glucose, serum insulin and c-peptide were higher in HFBA mice (P ≤ 0.05). Insulin stimulated suppression of glucose production (% ± SEM; HF = 38 ± 11, HFBA = 16 ± 16) was blunted in HFBA mice. Furthermore, fed-to-fasted expression of hepatic genes involved in lipid oxidation, including LCAD, MCAD, PPARa and CPT1a were significantly higher (P ≤ 0.05) in the HFBA mice. CONCLUSIONS: In summary, chronic BCAA supplementation induced hepatic lipid oxidation gene expression, without any apparent improvements in insulin sensitivity. In conclusion, while the induction of lipid oxidation by BCAAs could explain certain beneficial effects associated with their supplementation, the longer-term impact of the BCAAs on insulin sensitivity need to be further explored. FUNDING SOURCES: National Institutes of Health (NIH) grant RO1-DK-112865

OBJECTIVES: Epidemiological study results suggest that whole grain (WG) consumption is associated with a reduced risk of type 2 diabetes; however, the potential mechanism behind this observation is unclear. WG intake may lower postprandial glycemia and insulinemia and improve insulin sensitivity, thereby contributing to a reduced risk of type 2 diabetes. The objective of this systematic review and meta-analysis was to evaluate the impact of WG on postprandial glycemia and insulinemia and markers of glycemic control and insulin sensitivity/resistance. METHODS: A systematic review and meta-analysis was conducted on randomized controlled trials (RCTs) evaluating the effect of WG intake, compared to refined grain (RG) intake, on postprandial glycemia and insulinemia area under the curve and markers of glycemic control and insulin sensitivity/resistance in adults. A search of PubMed and Scopus yielded 80 relevant RCTs. Pooled estimates were expressed as standardized mean differences (SMD) between the WG intervention and RG control group. RESULTS: WG intake resulted in a significant reduction of postprandial glycemia (SMD: −0.46, 95% CI: −0.59, −0.33, P

OBJECTIVES: Most of the day is spent in the postprandial state, in part because of the additive effect of dietary fat from meals on triglycerides (TG), and this response is exacerbated by insulin resistance. However, 24-hr TG kinetics when consuming a realistic, Western diet (WD) remain poorly defined in at-risk individuals. The purpose of this exploratory case study was to compare postprandial 24-hr TG in 3 at-risk individuals defined as having normal-weight obesity (NWO), metabolic syndrome (MetS), and type 2 diabetes (T2D) consuming a WD. METHODS: 1 adult male from the following categories were recruited: NWO (i.e., 30% body fat and normal BMI), MetS (also a smoker), and T2D (taking 20 mg Atorvastatin). Upon arrival, a 24-guage indwelling catheter was inserted and a 0.9% NaCl drip initiated. Blood was drawn and TG measured hourly for 18-hrs and every 3-hrs for the last 6-hrs (Alere Cholestech; Hayward, CA). A semi-ad libitum WD (∼46% fat, 36% CHO, 18% protein) was provided consisting of breakfast (Jimmy Dean's), lunch 4-hrs later (McDonald's), dinner 5-hrs after lunch (Little Caesar's), and a snack 3-hrs after dinner (Blue Bell). Participants slept ≥ 6.5 hrs. RESULTS: As expected, all participants’ TG remained above fasting ≥ 75% of the 24-hr period and all exhibited peak TG between lunch and dinner. NWO presented with fasting TG of 100 mg/dL, and experienced peak TG of 278 mg/dL and area under the curve (AUC) of 3393 mg/dL. MetS similarly displayed a ∼3-fold increase in TG, although all TG parameters were lower (fasting = 69 mg/dL, peak = 214 mg/dL, AUC = 2772 mg/dL). Lastly, T2D closely resembled NWO with fasting TG of 100 mg/dL, peak TG of 282 mg/dL, and an AUC of 3165 mg/dL. CONCLUSIONS: In this case study, we observed that all 3 at-risk participants’ TG nearly tripled from baseline despite markedly different body composition, risk factors, and health status. NWO and T2D both had an adverse postprandial response per current guidelines (i.e., ≥ 220 mg/dL), but MetS was just below this mark. Surprisingly, NWO had a very similar TG response to T2D and the greatest AUC, although the statin very likely mitigated postprandial TG in T2D. Future, larger studies should seek to confirm our observation that a wide range of at-risk individuals experience a deleterious postprandial TG response during daily living when consuming a WD. FUNDING SOURCES: Internal Sources at Oklahoma State University

OBJECTIVES: Determine whether plasma omega-7 cis-vaccenic acid and palmitoleic acid levels are related to all-cause mortality in a general population. METHODS: Plasma phospholipids (PL) and triglycerides (TG) fatty acids were measured by gas chromatography with polar column and detected with a flame ionization detector in the Lifelines fatty acids cohort study participants (n = 864). Associations with all-cause mortality were analyzed by Cox proportional hazards regression with adjustment for conventional risk factors. RESULTS: During a median follow-up of 9.3 years, 33 (3.9%) participants died. Adjusting for typical risk factors, high levels of plasma PL and TG cis-vaccenic acid, and TG palmitoleic acid were found to be associated with all-cause mortality. A 1-SD increase in PL cis-vaccenic acid, TG cis-vaccenic acid, and TG palmitoleic acid was associated with increased risk of all-cause mortality with HRs (95% CI) of 1.69 (1.17–2.46), 1.54 (1.03–1.15), and 1.44 (1.08–1.92), respectively. Compared to the lowest tertile, the HRs (95% CI, p-trend) for the highest tertile of PL cis-vaccenic acid, TG cis-vaccenic acid, and TG palmitoleic acid were 3.0 (1.05–8.56, 0.03), 2.25 (0.87–5.85), and 3.39 (1.24–9.28, 0.02), respectively. CONCLUSIONS: Elevated levels of plasma cis-vaccenic acid and palmitoleic acid are risk factors for all-cause mortality. FUNDING SOURCES: The data analyses from the Lifelines Cohort that were carried out in this paper were funded by Friesl and Campina. The funders had no role in study design, data collection and analysis, manuscript preparation and decision to publish.

OBJECTIVES: To reveal alterations in metabolic pathways in response to an oral glucose tolerance test (OGTT) underlying the development of insulin resistance during the pubertal transition. METHODS: Participants were recruited as healthy controls (HC, n = 55, aged 8.3–18.0 years, BMI percentile 5–85%) and overweight and obese individuals (OVOB, n = 228, aged 8.1–17.9 years, BMI percentile ≥ 85%). Participants were grouped based on their peak insulin response to the OGTT, stratified by peak at t30 (Group 1, n = 163), t60 (Group 2, n = 75), and t120 minutes (Group 3, n = 44). Untargeted metabolomics profiled 267 annotated metabolites and > 3000 unannotated features in plasma at t0 and t60 minutes. Regression classified changes in metabolites across the time-course, assessing the influence of BMI and insulin response (FDR

OBJECTIVES: Kappa-Carrageenan(CGN) is a widely used food additive in the meat industry and a highly viscous soluble dietary fiber which can hardly be fermented. It has been shown to be able to regulate the energy metabolism and inhibit diet-induced obesity. However, the mechanism is not well understood. The purpose of this study is to investigate the mechanisms of κ-carrageenan to inhibit the body weight gain. METHODS: A high-fat diet incorporated with lard, pork protein and CGN (2% or 4%, w/w) was given to C57BL/6J mice for 90 days. The energy intake and weight changes were measured every three days. After the dietary intervention, mice were sacrificed, liver and epididymal adipose tissues were taken for real-time polymerase chain reaction (RT-qPCR) analysis. RESULTS: The CGN in the high-fat diet restricted weight gain by decreasing liver and adipose mass without inhibiting energy intake. The genes involving energy expenditure such as Acox1, Acadl, CPT-1A and Sirt1 were upregulated in the mice fed with carrageenan. However, the genes responsible for lipid synthesis were not significantly different compared to the diet-induced obese model. CONCLUSIONS: The anti-obesity effect of the CGN in high-fat diet could be highly related to the enhancement of energy expenditure through up-regulating the downstream genes which promote β-oxidation by increasing the Sirt1 gene expression in liver. FUNDING SOURCES: Ministry of Science and Technology of the People's Republic of China (10000 Talent Project)

OBJECTIVES: Serum erythritol is a predictive biomarker of chronic disease development and complications. In cohort studies, elevated serum erythritol at baseline was predictive of central adiposity gain, T2DM, and cardiovascular disease development up to 20 years later. Erythritol is a polyol that has been well characterized as a non-nutritive sweetener. Erythritol was recently discovered to be synthesized endogenously in humans from glucose through the pentose phosphate pathway (PPP). The regulation of erythritol synthesis in mammals, however, is not characterized. The purpose of this study was to assess stimuli that modulate intracellular erythritol levels and the distribution of erythritol in key metabolic tissues. METHODS: First, we fed 8-week-old C57BL/6J mice a defined diet (AIN93G) for two weeks, after which plasma and tissue erythritol were measured by GC-MS. To further evaluate the cellular regulation of erythritol synthesis, we used A549 cells for their high PPP activity. Using siRNA, we knocked down SORD (a potential erythritol-synthesizing enzyme) and glucose-6-phosphate dehydrogenase (G6PD) under normal (5 mM) and high (25 mM) glucose conditions and measured intracellular erythritol. We also exposed A549’s to hydrogen peroxide to assess if erythritol synthesis is elevated by oxidative stress, an additional stimulator of the PPP. RESULTS: Plasma erythritol ranged from 0.44 uM to 0.73 uM in young, healthy mice. Erythritol differed significantly based on tissue type (p

OBJECTIVES: Okara is a fiber-rich food processing by-product. However, it is underutilized as food due to its rapid putrefaction and poor sensorial properties. Valorization via fermentation (biovalorization) can alleviate its undesirable qualities while augmenting its soluble fiber content. The increase in soluble fiber may improve postprandial glycemic and insulinemic responses, potentially via generation of short-chain fatty acids (SCFAs) from colonic bacteria fermentation. This study aimed to assess the effect of consuming okara and biovalorized okara-containing biscuits on postprandial glucose, insulin and SCFAs responses in older Singaporeans. METHODS: Fifteen healthy middle-aged and older Singaporeans participated in a randomized controlled crossover trial. Subjects underwent a 4-hour mixed meal tolerance test with 100 g ingestion of 3 types of biscuits – control (C, no okara), biovalorised okara (RO) and autoclaved okara (AOK). RO and AOK biscuits were produced by 20% substitution of wheat flour with okara powder that was fermented with Rhizopus oligosporus (7% w/w) or autoclaved. The 4-hour incremental area under the curve (iAUC) of glucose, insulin and SCFAs (acetate, propionate and butyrate) were assessed. β-cell function was evaluated based on glucose stimulated insulin secretion, using a ratio of 4-hour AUC of insulin to glucose. Estimated insulin sensitivity (ISI) and metabolic clearance rate (MCR) were assessed with Stumvoll Index. RESULTS: Although no difference in glucose response was noted, RO showed significantly lower insulin iAUC (RO: 8931 ± 1058 mU/L × min, mean ± SE; C: 10271 ± 866 mU/L × min, p = 0.021) and improved β-cell function (p = 0.028) compared to C. AOK yielded significantly greater ISI and MCR compared to C (p(ISI) = 0.016, p(MCR) = 0.009) while RO showed no difference against AOK or C. Significantly higher acetate and total SCFAs iAUC were evident for both RO and AOK relative to C (C vs RO: p(acetate) = 0.012, p(total)(SCFA) = 0.001; C vs AOK: p(acetate) = 0.015, p(total)(SCFA) = 0.001). AOK also had significantly greater propionate and butyrate iAUC compared to C (C vs AOK: p(acetate) = 0.002, p(butyrate) = 0.001). CONCLUSIONS: Consumption of okara and biovalorized okara-containing biscuits offers the benefit of attenuating postprandial insulinemic response possibly via SCFAs modulation. FUNDING SOURCES: Singapore Ministry of Education

OBJECTIVES: There is persistent controversy over the extent to which different components of energy expenditure disproportionately decrease after weight loss and contribute to weight regain through decreased energy requirements. We conducted a secondary analysis of the CALERIE I study to test the hypothesis that decreased resting metabolic rate (RMR) and energy expenditure for physical activity (EEPA) after a 6-month calorie restriction intervention would predict weight regain at 12 months, with a greater decrease in RMR than EEPA. METHODS: Participants (n = 46) received all food and energy-containing beverages for 6 months. Outcome measures included total energy expenditure by doubly labeled water, RMR by indirect calorimetry, and body composition by BOD POD. Predictions for RMR and EEPA were derived from baseline linear regression models including age, sex, fat mass, and fat free mass. Baseline regression coefficients were used to calculate the predicted RMR and EEPA at 6 months. Residuals were calculated as the difference between measured and predicted values and were adjusted for body weight. The presence of metabolic adaptation was evaluated by a paired t-test comparing measured and predicted RMR at 6 months. Differences between 6-month RMR and EEPA residuals were evaluated by the same method. Linear regression was used to assess the association between 6-month residuals and weight loss maintenance (% weight change, 6 to 12 months). RESULTS: Mean weight loss was 6.9% at 6 months with 2.1% regain from 6 to 12 months. No adaptation in RMR was observed at 6 months (mean residual: 19 kcal; 95% confidence interval: −9, 48; P = 0.18). However, significant adaptation was observed in EEPA (mean residual: −199 kcal; −126, −272; P

OBJECTIVES: We investigated the impact of mTOR complexes inhibition with RapaLink-1, a third-generation bivalent mTORC1/mTORC2 inhibitor that links rapamycin with a mTOR-kinase inhibitor, or Torin-2 (ATP-competitive) on mitochondrial dynamics, bioenergetics, and extracellular flux. METHODS: We used insulin-secreting, glucose-responsive pancreatic beta cells derived from transgenic mice expressing SV40 (Beta-TC-6 cells, ATCC-11506). Cells were treated for 24 hours with either: RapaLink; Torin-2; rapamycin; metformin; a combination of metformin and RapaLink, or Torin-2; compared to vehicle control. Bioenergetic dynamics and cellular metabolism were quantified using MitoStress Test XF24 (Agilent, Seahorse). The real-time, live-cell approach simultaneously measures oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) to determine cellular respiration and metabolism. Statistical significance was assessed by ANOVA followed by an unpaired t-test. RESULTS: Rapalink-1 and Torin-2 incubation decreased basal OCR compared to rapamycin alone or vehicle control (189.58 ± 48.58, 116.85 ± 26.55 versus 405.01 ± 21.57, 444.19 ± 58.59, p

International audience; Abstract Objectives We aimed to characterize the effects of a low dose of a sustained-release L-arginine (L-ARG) supplementation on plasma metabolome in healthy overweight adults with cardiometabolic risk factors, and study if its effect could improve the capacity to handle a high fat-high sugar meal, that deeply and acutely challenge metabolic capacities. Methods In a randomized, double-blind, controlled trial, 33 healthy overweight adults (BMI > 25kg/m²) with cardiometabolic risk (plasma triglycerides > 150 mg/dL; waist circumference > 94 cm (men) or > 80 cm (women)) were treated with 1.5 g L-ARG 3 times/d (4.5 g/d) or placebo for 4 weeks. On the last day of treatment, the volunteers consumed a high fat, high sugar meal challenge (900 kcal). Plasma was collected at fasting and 2, 4 and 6 h after the meal. Metabolites were analyzed by high-resolution mass spectrometry hyphenated to liquid chromatography, using reversed and normal phase columns, and operated in both positive and negative ionization modes. Annotation was performed using an in-house database referencing more than 1300 metabolites. Metabolic profiles were analyzed using Linear Mixed Models-PCA (LiMM-PCA), which enables to analyze repeated multivariate data. LiMM-PCA combines linear mixed models and PCA to assess the effects of both fixed factors (Treatment, Time before and after meal, interaction Treatment x Time, Order of treatment administration and Period of the study) and random factors (Individual). Results 521 metabolic features were identified in the plasma. Time accounted for most part of the variance in dataset (30.0%, P 0.10). The analysis of the metabolites contributing the most to these effects is under progress. Conclusions L-ARG supplementation has a significant effect on the metabolome in a situation where the metabolome is heavily impacted by a large allostatic load, and these two effects are independent of each other. Funding Sources Supported by a grant from Pierre Fabre Research Institute.

International audience; Objectives In the current context of finding plant alternatives to animal proteins, pea would be a good option regarding its high protein content and its well-balanced amino acid (AA) profile. However, we must examine its digestibility, a main criteria of protein nutritional quality. The aim of this study was to determine the real ileal AA and nitrogen (N) digestibility (RIDAA and RIDN) of pea protein as compared to milk casein in humans. We also evaluated their respective nutritional qualities through the calculation of the digestible indispensable amino acid score (DIAAS) and the net postprandial protein utilization (NPPU). Methods Fifteen healthy adult volunteers completed the study and were equipped with a triple-lumen naso-ileal tube. They were given 9 portions of mashed potatoes containing either pea protein or casein isolates that were intrinsically labelled with 15N. PEG-4000 was perfused in the ileum as a non-absorbable marker to measure the intestinal flow rate. Ileal digesta were collected continuously by aspiration with a syringe over an 8-h postprandial period, while plasma and urine were sampled regularly. N and AA contents of digesta and protein isolates were measured using EA and U-HPLC. PEG-4000 content of the digesta was measured by turbidimetric method. Urea was extracted from plasma and urine samples. 15N enrichment was assessed in digesta, urea and protein isolates by EA-IRMS and in individual AAs by GC-C-IRMS. Results Mean RIDAA was 93.6 ± 2.9% and 96.8 ± 1.0% for pea protein and casein, respectively, with no significant difference between groups (P = 0.22). RIDN was 92.0 ± 2.7% and 94.0 ± 1.7% for pea protein and casein, respectively, and were not different (P = 0.11). The DIAAS was 1.00 for pea protein and 1.45 for casein. The NPPU was 67.0 ± 6.2% for pea protein and 70.7 ± 1.9% for casein and the difference was not significant (P = 0.15). Conclusions Overall, the bioavailability was not different between pea protein and casein in healthy adults. The DIAAS of pea protein reached 1, revealing the absence of limiting AA in regard to the requirements. Considering its AA composition and the digestibility results we obtained, pea protein can be qualified as a high-quality protein. Funding Sources Roquette

OBJECTIVES: Linoleic acid (LA) is the major fatty acid in cardiolipin (CL), a phospholipid important for mitochondria function. Increasing dietary LA elevates tetralinoleoyl CL (LA(4) CL) in cardiac muscle of animals; however, it is not clear if dietary LA increases LA(4) CL in humans. The aim of this study was to determine if daily consumption of a cookie made with a LA-rich oil for two weeks could alter LA(4) CL in peripheral blood mononuclear cells (PBMC) in healthy adults. METHODS: In a double-masked placebo-controlled study, 84 healthy adults were randomly assigned to consume one cookie made with LA-rich grapeseed oil (LA-cookie) or one cookie made with oleic acid-rich (OA) safflower oil (OA-cookie), every day for two weeks. Fasting blood samples were collected for analysis of PBMC cardiolipin species. RESULTS: Daily consumption of the LA-cookie for 2 weeks increased LA(4) CL in PBMC, while consuming the OA-cookie did not alter LA(4) CL (group x week interaction p

OBJECTIVES: Approximately 50–80% of cancer patients suffer from cachexia represented by weight loss mainly due to loss of skeletal muscle. Cancer-induced cachexia is a complex metabolic syndrome associated with not only systemic inflammation but also perturbations to energy metabolism. In this study, we profiled gene expression patterns of different organs in CT-26 tumor bearing mice in order to understand metabolic dysfunction in cancer cachexia. METHODS: The transcriptomic profiles of skeletal muscle, adipose tissue, and liver of CT26-tumor bearing mice were generated using SurePrint G3 Mouse Gene Expression 8 × 60 K v2 (Agilent, Inc.). Functional and network analyses were performed using Gene Set Enrichment Analysis and Ingenuity Pathway Analysis (QIAGEN). RESULTS: We identified 299, 508, and 1,311 genes differentially regulated in skeletal muscle, adipose tissue, and liver, respectively. In the skeletal muscle, lipid biosynthetic process and mitochondrial electron transport were negatively regulated and network involved in glutamine metabolism was up-regulated. In adipose tissue, tricarboxylic acid cycle was down-regulated and lipid metabolism was associated with several genes including Thrsp, Plvap, and Sphk1. In the liver, regulation of gluconeogenesis was down-regulated, while production of lactic acid and uptake of D-glucose were related with H6pd and Pkm whose expression was up-regulated during cancer cachexia. Furthermore, the top network matched by genes commonly up-regulated in all organs included Bcl3, Csf2rb, Fcgr2a, and Lilrb3, which are known to be associated with inflammation and muscle wasting. CONCLUSIONS: Our data suggest that skeletal muscle, adipose tissue, and liver present distinct gene expression profiles associated with inflammation and energy metabolism and several genes up-regulated in all organs might be candidate biomarkers for the prevention and early detection of cancer cachexia. FUNDING SOURCES: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education.

OBJECTIVES: Review human intervention trials that investigated the effects of linoleic acid (LA), the essential omega-6 polyunsaturated fatty acid (PUFA), on lipid risk markers for cardiovascular disease (CVD) in healthy individuals. These major lipid risk markers include high serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), very-low density lipoprotein cholesterol (VLDL-C), triglycerides (TGs), and low serum concentrations of high-density lipoprotein cholesterol (HDL-C), as well as lipoprotein(a), apolipoprotein A1 (associated with HDL), and apolipoprotein B (associated with LDL). The mechanisms by which LA affects these lipid risk markers and dietary recommendations for LA in decreasing lipid risk markers are discussed. METHODS: PubMed was used to search for peer-reviewed journal articles on the effects of LA on lipid risk markers for cardiovascular disease in healthy individuals. The search process took place from April to June of 2020. Articles were included if the amount of LA consumed, in grams or percentage of energy, was discussed in relation to cardiovascular disease during an intervention trial. Observational, postprandial and animal studies were excluded. RESULTS: According to reviewed human intervention trials, the following were the major findings: 1) LA decreased total cholesterol compared to diets not containing significant amounts of PUFAs; 2) LA decreased LDL-C compared to saturated fatty acids; 3) LA decreased VLDL-C compared to oleic acid, a monounsaturated fatty acid (MUFA); 4) there were inconsistent results regarding LA consumption on TGs; and 5) HDL-C did not differ compared to oleic acid. CONCLUSIONS: A dietary strategy to decrease CVD risk factors is to replace a portion of saturated fatty acids with MUFAs and PUFAs. To our knowledge, this is the first review to demonstrate that consumption of LA decreases lipid risk markers for CVD in healthy individuals during intervention trials. Therefore, it is recommended to incorporate adequate sources of LA, such as vegetable oils, nuts, and seeds into the diet to decrease lipid risk markers for CVD. FUNDING SOURCES: No funding was used for this project.

OBJECTIVES: The efficacy of oat beta-glucan (OBG), a viscous soluble fibre, on postprandial glycemic outcomes may depend on the nature of the control and the dose and molecular weight (MW) utilized. We undertook a systematic review and meta-analysis of acute clinical trials to determine whether these features mediate the glycemic and insulinaemic responses to OBG. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through October 27, 2020. We included acute, single-meal feeding, controlled trials investigating the effect of OBG (concentrate or oat bran) added to a carbohydrate-containing meal compared to a comparable meal (matched control) or a different carbohydrate-containing meal (unmatched control). Two reviewers extracted the data and assessed the risk of bias and certainty of evidence (GRADE). The primary outcome was incremental area under the curve (iAUC) for blood glucose. Data were pooled using the generic-inverse variance method with random effects model and expressed as ratio of means with [95% Cis]. RESULTS: One hundred and three trial comparisons (N = 538) were included. OBG reduced glucose iAUC and iPeak by 23% (0.77 [0.74, 0.81]) and 28% (0.72 [0.64, 0.76]) and insulin by 22% (0.78 [0.72, 0.85]) and 24% (0.76 [0.65, 0.88]), respectively. Dose, molecular-weight and comparator were significant effect modifiers of glucose iAUC and iPeak. Significant linear dose-response relationships were observed for all outcomes. OBG molecular-weight > 300 kg/mol significantly reduced glucose iAUC and iPeak, whereas, molecular-weight

OBJECTIVES: Obesity is caused by an imbalance between energy intake and energy expenditure. Resting energy expenditure (REE) represents the calories burned at rest and accounts for > 60% of total energy expenditure. Energy expenditure plays an important role in obesity development, hence an increase in REE could facilitate body weight reduction. Capsaicinoids, extracted from capsicum annuum have been known to increase metabolism, lipolysis & induce satiety. The study objective was to evaluate the effects of Capsimax™ on REE and thermal sensation. METHODS: This was a randomized, double-blind, placebo controlled, cross-over study. Efficacy analysis included subsets of 17 males and 7 females who received single dose of Capsimax™ 100 mg (2 mg total capsaicinoids) and placebo in a cross-over fashion with washout period of 3–6 days as per randomization schedule. REE was measured using Cosmed Q-NRG by indirect calorimetry. Secondary objectives were Area under curve (AUC) for REE, VO2, VCO2 & subject's innate thermal sensation using American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) scale. REE, VO2, VCO2, ASHRAE scale were evaluated at 0 (pre-dose), 1, 2, 3 & 4 hours and additional measures for ASHRAE scale at 0.5 & 1.5 hours post-dose. Safety was assessed throughout the study with measurements of ECG, blood pressure, pulse rate, body temperature & adverse event occurrences. RESULTS: In males, Capsimax(TM) consumption significantly increased (p

OBJECTIVES: We examined the effects of dietary butyrate, a short-chain fatty acids (SCFAs) on body weight control and metabolism in a diet-induced obesity rat model. METHODS: Male Sprague-Dawley rats fed with high-fat diet for 14 weeks. Sodium butyrate was administrated through diet supplementation at 3% wt/wt for long-term (14 weeks) or drinking water at 1% for short-term (2 weeks). Serum and feces were collected. Colon and liver tissues used for analyzing mRNA expression. To assess the effects of butyrate on lipid metabolism, 3T3-L1 cells were treated with sodium butyrate and sodium-3-hyroxybutyrate during adipogenic differentiation. RESULTS: On the high-fat diet, dietary supplementation of butyrate protected against body weight gain. Interestingly, food intake was increased and consistently colonic Proglucagon (Gcg), encoding Glucagon-like Peptide-1 (GLP-1) involved in appetite-suppression, was decreased. In contrast, short-term administration of butyrate did not affect body weight and food intake. Free fatty acid receptor 2 (Ffar2), a G-protein coupled receptor recognizing SCFAs and stimulating GLP-1 production, was decreased in colon. The colonic Hydroxycarboxylic acid receptor 2 (Hcar2) and Tight junction protein-1 (Tjp1) marginally increased but expression of inflammatory cytokines was not altered, implicating that anti-obesity effects of butyrate were not primarily through colon. In the liver, butyrate showed significantly decreased Ffar2 and Peroxisome proliferator–activated receptor-γ (Ppar-γ). In the butyrate group, aberrant phenotypes were observed including hyperlipidemia and alteration of serum level of adiponectin without change in fecal energy density. Intriguingly, in the 3T3-L1 cell line, fat accumulation was significantly stimulated at lower concentration of butyrate with elevated expression of Ffar2 and Ppar-γ. High concentration of butyrate reduced Ffar2 and Ppar-γ and suppressed adipocytic fat accumulation. CONCLUSIONS: Our results suggested that dietary butyrate prevented diet-induced obesity despite increased food intake. Moreover, butyrate may regulate lipid metabolism in a dose-dependent manner. FUNDING SOURCES: This research was supported by Basic Science Research Program through the NRF funded by the Ministry of Education. J.S is grateful for financial support from Hyundai Motor Chung Mong-Koo Foundation.

OBJECTIVES: Dietary protein intake augments muscle protein synthesis rates during acute recovery from resistance exercise training (RET) and can help offset age-related loss in muscle mass. Skeletal muscle tissue contains a variety of different protein pools such as myofibrillar (contractile), mitochondrial (substrate oxidation), and collagen (structural support) proteins that have been reported to have different contraction and nutrient sensitivities in controlled laboratory studies. However, no study has investigated the impact of dietary protein intake on the synthesis of these specific muscle proteins fractions during RET in a free-living setting. Therefore, we investigated the effect of dietary protein intake on daily muscle protein synthesis rates (PS) within the myofibrillar (MyoPS), mitochondrial (MitoPS), and collagen (CPS) protein fractions throughout the early phase (0 – 3 wks) of RET in middle-aged adults. METHODS: Twenty middle-aged adults (47 ± 1 y, BMI 28 ± 1 kg/m(2), M = 12, F = 8) were stratified and randomized to consume either moderate (MOD; 1.06 ± 0.22 g/kg/d) or high (HI; 1.55 ± 0.25 g/kg/d) amounts of protein during a dietary counseling-controlled resistance training program. On day 0, participants ingested intermittent boluses of deuterated ((2)H) water followed by daily maintenance doses throughout the study period. Muscle biopsies were collected prior to and at weeks 1, 2, and 3 of the intervention to assess MyoPS, MitoPS, and CPS by LC/MS. RESULTS: MitoPS decreased at 0–3 wks when compared to 0–1 wks (P = 0.010, CI: −0.77 – −0.10%/d) regardless of group (HI: 0.64 ± 0.32%/d and MOD 0.86 ± 0.55%/d; P = 0.827). A similar decline was also observed for CPS (group P = 0.323; time P = 0.007). The MyoPS in the HI condition remained constant (0–1 wk: 0.81 ± 0.42%/d and 0–3 wks: 0.81 ± 0.72%/d, P = 1.0), but MOD decreased over time (0–1 wk: 1.35 ± 0.9%/d and 0–3 wks: 0.77 ± 0.43%/d, P = 0.023). CONCLUSIONS: Our results demonstrated that additional protein intake above moderate amounts does not meaningfully potentiate the stimulation of longer-term muscle protein synthetic responses within the myofibrillar, mitochondrial, or collagen protein fractions during the early stages of a RET in middle-aged adults. FUNDING SOURCES: Funded in part by the Beef Checkoff. AFS funded by CAPES Scholarship.

International audience; Objectives The availability of indispensable amino acids (IAA) modulates protein turnover. More particularly AAI deficiency reduces protein synthesis while the consequence on proteolysis remains unclear. The present study aims to evaluate the specific response of both protein synthesis and proteolysis to a diet restricted on one strictly indispensable IAA, either lysine or threonine Methods Sixty-four growing rats were divided into 8 groups (n = 8/group). They were fed for 3 weeks isocaloric diets composed with different levels of lysine or threonine (L or T), 15, 25, 40, 60, 75, 100 or 170% of the theoretical lysine/threonine requirements. At the end of the experiment, rats were injected with valine13C and tissues and biological fluids were collected for gene expression measurement and blood amino acids (AA). Protein synthesis rate (Fractional and Absolute rate synthesis, ie FSR, ASR) were determined in liver and muscle. Statistical analysis was done by 1- or 2-factor ANOVA, when data were repeated. Results Severe (L/T15, L/T25) and moderate (T40) lysine or threonine deficiency resulted in a decrease in body weight gain due to a decrease in lean body mass. Severe restriction (L15, T15, T25) decreased the muscle FSR whereas no effect was observed in the liver. When the rate of protein synthesis was expressed per tissue, the ASR was decreased by severe restriction of lysine and threonine in liver and muscle and by moderate threonine deficiency (T40, T60, T75) in muscle. In liver, no effect of lysine and threonine on proteolysis was observed. In muscle, only severe lysine (L15) deficiency increased proteolysis. Dietary lysine deficiency induced a decrease in lysine concentration in the portal vein and in the vena cava whereas for threonine deficiency, all AAIs except threonine were decreased in the portal vein and vena cava. Conclusions These results indicate that the decreased protein synthesis is the primary mechanism involved in decreased lean body mass in response to the severe deficiency in a single AAI. Deficiency of a single AAI reproduce the effect of the low protein diet on protein synthesis. Lysine and threonine deficiency differently affect for a part protein turnover probably in relation with the tissue where they are metabolized. Funding Sources This study was funded by the doctoral school ABIES and AlimH-INRAE department.

OBJECTIVES: Branched chain amino acids (BCAAs), Valine, Leucine, and Isoleucine have been shown to impact adipose tissue physiology through regulation of adipocyte differentiation, lipogenesis, and lipolysis. Further, circulating BCAAs are elevated during obesity and insulin resistance, a characteristic attributed to impaired BCAA catabolic networks in adipose tissue and skeletal muscle. The objective of this study was to determine whether the induction of lipolysis in adipose tissue is a characteristic feature prompted by the chronic availability of BCAAs. METHODS: Mice (C57-BL6N) were kept on low-fat (LF, 10% fat calories; n = 9) and low-fat supplemented with 150% BCAA (LB; n = 10) diets for 34 weeks. Following an overnight fast (∼12–14 hrs), serum and perigonadal adipose (PGA) tissue samples were collected for metabolic analysis. Serum free fatty acids (FFAs) were analyzed and 25 milligrams (mg) of PGA was used for an in vitro lipolysis assay. Lipolysis in the PGA was induced under basal and isoproterenol (ISP, 10 micromolar, μM) stimulated conditions for 2 hours. In a second experiment, PGA tissue explants from normal mice (n = 18) were incubated with two levels of BCAA supplementation (500 μM and 1 millimolar, mM). FFAs in the incubation media were measured as an index of adipose tissue lipolysis. RESULTS: Overnight fasting body weights of the LF and LB mice remained similar. However, PGA tissue weights were significantly lower in the LB group (grams ± SEM; LF, 1.34 ± 0.09 vs LB, 0.84 ± 0.11, P = 0.003). LB serum FFAs were elevated (mM FFAs ± SEM; LF 0.73 ± 0.04 vs LB, 0.88 ± 0.04, P = 0.01). Basal lipolysis (mM FFAs/mg tissue protein ± SEM) trended to be higher in the PGA from the LB animals (LF, 1.44 ± 0.18 vs LB, 1.88 ± 0.15, P = 0.08). While ISP significantly induced lipolysis, the stimulated lipolytic rates remained similar between LF and LB groups. When normal PGA explants were challenged with BCAAs, the 1mM BCAA supplemented group tended to show higher fatty acid release (mM FFAs/mg tissue protein ± SEM; 500 μM, 0.89 ± 0.06 vs 1mM, 1.02 ± 0.05, P = 0.09). CONCLUSIONS: In summary, these results suggest that BCAA mediated increases in adipose tissue lipolysis can contribute to circulating FFA levels. BCAA mediated lipolysis and the subsequent increase in circulating FFAs could indirectly modulate substrate oxidation in peripheral tissues including liver and muscle. FUNDING SOURCES: NIH RO1

OBJECTIVES: Epigenetic is one of the possible mechanisms of transmit parental metabolic stress to offspring. tRNA modification or fragmentation is a promising candidate. We investigated the molecular mechanism of intergeneration transmission of diet-induced metabolic stress. METHODS: Male mice fed with control diet (CD) or high-fat diet (HFD) for 9 weeks. Body weight, amount of food intake and organ weights were measured. Metabolism-related proteins and gene expression were measured in testis and liver. tRNA methylation in sperm was investigated by bisulfite conversion-based sequencing. We analyzed publicly available omics data to profile changes of high-fat diet feeding. To explain mTOR activity linked to angiogenin (ANG) gene expression, we treated compound C (CC) or rapamycin (RP) in cell lines. RESULTS: We showed mTOR negative regulators were down regulated in HFD from analysis of transcriptome data from liver and sperm. Consistently, analysis on sperm metabolome data revealed that free amino acid level and tRNA amino-acyl biosynthesis pathway was up-regulated in HFD. Increased a level of phospho-mTOR protein was confirmed in testis, but not phospho-AMPK protein. Next, we measured tRNA modification-related gene expression levels in testis and liver. Expression of Dnmt2 and NSun2 related in tRNA methylation was elevated in HFD in testis and liver. However, expression of ANG related with tRNA cleavage was only increased in testis. In addition, methylation status in sperm tRNA-Asp-GTC was no different between diets. The data suggested that tRNA cleavage with ANG, rather than tRNA methylation process, was more likely involved in transmit transgenerational effect to offspring. Finally, we investigated changing mTOR activity could affect to Angiogenin gene expression level. Treatment with CC showed increased Angiogenin gene expression level, but RP treatment showed no change. CONCLUSIONS: Our data suggested that diet-induced alteration of mTOR activity led to upregulation of Angiogenin expression in sperm, which might be a key of transgenerational mechanism. FUNDING SOURCES: This study was supported by the National Research Foundation of Korea the Korean National Cancer Center. EL is grateful for financial support from Hyundai Motor Chung Mong-Koo Foundation and BK21 FOUR (Fostering Outstanding Universities for Research).

OBJECTIVES: The protein quality digestible indispensable amino acid scores (DIAAS) require determination of amino acid (AA) bioavailability, which is often quantified as the net disappearance of dietary AAs at the end of the small intestine, so-called true ileal digestibility. It is often assumed that bioavailability is mainly influenced by protein breakdown and that free AAs are completely absorbed by the small intestine. However, some studies report substantial amounts of free AAs in the unabsorbed protein fraction present in terminal ileal digesta. This study quantified free AAs in ileal digesta of humans and pigs and estimated their impact on AA bioavailability. METHODS: Two studies were performed with 3 diets, i.e., zein, whey or protein-free. In study 1, ileal digesta of 8 human ileostomates was collected over 9 hours after ingestion of a single meal. In study 2, 12 pigs were fed 7 days with one of the 3 diets and ileal digesta was collected over 9 h on the last 2 days according to a standardized digestibility protocol. Total and free AA content were analyzed in ileal digesta. RESULTS: All ileal digesta contained free AAs. If the analyzed free AAs would have been absorbed in the small intestine the bioavailability for whey, which was > 95%, would only increase 0.4%-unit on average for the different AAs in humans and 0.1%-unit in pigs. For zein protein, which is ∼70% bioavailable, the impact of unabsorbed free AAs on bioavailability was on average 2.3 ± 1.2%-unit in humans and 3.5 ± 5.1%-unit in pigs. In both species, the biggest impact was seen for the free essential AA threonine; its potential absorption could increase threonine bioavailability of zein by 6.6 ± 4.0%-units for humans and 6.6 ± 8.6%-units for pigs. Moreover, for both species the proportion of threonine in free form, relative to total threonine, was significantly higher in ileal digesta after ingestion of zein compared to whey or the protein-free condition (p

International audience; Objectives The global demand for protein is growing and it seems mandatory to find alternatives to animal proteins that are of good nutritional quality, implying a good digestibility. Legumes are potential candidates, as their indispensable amino acid (IAA) profile is relatively balanced. The aim of this study is to compare the protein and AA ileal digestibility of pea protein and casein in humans using ileal sampling and intrinsically labelled proteins. Methods Sixteen healthy volunteers were intubated and were given twelve doses of mashed potatoes containing either pea protein or milk casein isolates. The proteins were intrinsically labelled with 15N. Polyethylene glycol (PEG) was perfused as a non-absorbable marker to measure the intestinal flow, and ileal digesta were collected during 8 hours after the ingestion of the first meal. PEG content was assessed using a turbidimetric assay. Real ileal nitrogen (N) digestibility was measured by assessing N content and 15N enrichment by EA-IRMS and calculated as follows: $$\begin{eqnarray} \begin{array} \text{Ileal fiow (mL/30 min)} &=& \rm{[PEG]_{solution}/[PEG]_{digesta}}\\ &&\times \text{ infusion rate} \times \rm{time} \end{array} \end{eqnarray}$$$$\begin{eqnarray} \begin{array} \text{Exogenous N fiow (mmol/30 min) } &=& \rm {N_{exo} = (\% DM \times \%N)}\\ &&/(14 \times 10) \times \text{ileal fiow} \times \rm{APE_{digesta}/APE_{meal}} \end{array} \end{eqnarray}$$$$\begin{eqnarray} \rm{Digestibility\ (\%)} = (\rm{N_{ingested} - N_{exo} / N_{ingested} \times 100}) \end{eqnarray}$$$$\begin{eqnarray} \text{WithDM = DryMatterofdigesta, APE = AtomPercentExcess} \end{eqnarray}$$ Results The first results were obtained on 7 subjects that were given pea protein (N = 3) or milk casein (N = 4). The mean ileal flow for all the volunteers was 1.83 ± 0.70 mL/30 min (mean ± SD), and was quite stable over time. The total N exogenous flow was 15.50 ± 5.83 mmol for pea protein and 13.56 ± 3.48 mmol for casein. The true ileal N digestibility was 95.40 ± 1.73% for pea protein and 95.42 ± 1.17% for casein. Ileal IAA digestibility is in progress. Conclusions The intermediate results show no difference between pea protein and casein in terms of ileal digestibility, suggesting that pea protein could be a promising plant-based alternative. AA digestibilities and data from the remaining 9 volunteers to be tested will complete the study. Funding Sources Roquette.

OBJECTIVES: The aim of this study was to evaluate the digestibility of casein and its amino acids (AA) in rats of different ages (2 months vs 11 months) and adiposity levels (normal vs high). METHODS: Wistar rats of 1 month (n = 15) and 10 months (n = 15) at their arrival were fed ad libitum for 28 days either with a standard diet (14% P/E, 75% C/E, 11% L/E) or a Western diet (14% P/E, 51% C/E, 35% L/E) in order to obtain respectively rats of normal and high adiposity levels. Four groups were constituted (n = 7/8): 2 months/normal adiposity (2 M/NA), 2 months/high adiposity (2 M/HA), 11 months/normal adiposity (11 M/NA) and 11 months/high adiposity (11 M/HA). After a week on the standard diet, the rats consumed a 4 g meal containing (15)N labeled casein (Prodiet® 85B). Blood samples were taken at t = 0, t = 1 h, t = 3 h after meal consumption, and the rats were euthanized at t = 6 h. Digestive contents were collected and body composition was determined. Nitrogen quantity and (15)N enrichment were analyzed in the meal and digestive contents by EA-IRMS, allowing for the estimation of casein digestibility. Concentrations in AA and their (15)N enrichments were determined respectively by UHPLC and GC-C-IRMS to obtain the digestibility of individual AA. RESULTS: Weight did not differ between groups of the same age, but body composition analysis showed a significant difference in adiposity (P = 0.0008 between the 2 M groups; P = 0.0004 between the 11 M groups). Nitrogen fecal digestibility of casein increased significantly in rats with higher adiposity levels (2 M/NA = 94.1 ± 1.1%; 2 M/HA = 95.2 ± 1.7%; 11 M/NA = 94.5 ± 2.2% for 11 M/HA = 95.9 ± 0.7%; P = 0.0339). No difference was found in the digestibility of individual AA. 6 hours after meal ingestion, there was significantly more exogenous nitrogen in the stomach of rats aged 11 months compared to those of 2 months (3,9 ± 6,9% for the 2 M groups and 11,3 ± 9,2% for the 11 M groups P = 0.0188;). Except for methionine, there was no difference in plasma concentration levels of essential AA over time between the groups. CONCLUSIONS: Our results suggest that age slows down digestion, in accordance with the literature. We showed that adiposity increased casein digestibility but without any effect at the level of individual AA digestibility. FUNDING SOURCES: Ingredia.

OBJECTIVES: Complex food structures can act like barriers towards digestive enzymes and reduce nutrient bioavailability. Nutrients that escape digestion in the upper gut (mainly fibre), becomes available for bacterial fermentation in the distal gut and generates short chain fatty acids (SCFA) which stimulate the release of appetite suppressing hormones Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY). Processing can alter food structures, leading to more digestible products, but reducing nutrients reaching the distal gut, fermentation and appetite suppression. This study aimed to investigate the impact of food structures on the level of carbohydrate reaching the distal ileum and its subsequent effect on SCFA production and appetite hormone release. METHODS: Healthy volunteers (n = 10, 18–65 years) attended three separate 4-day inpatient visits. A nasoenteric tube was inserted into their distal ileum. During each visit, participants had one of three dietary interventions: Low fibre, processed diet (LF); High fibre, unprocessed diet (HF); same as HF but domestically processed (HFP). On day 4, ileal, blood and breath hydrogen (BH) samples were collected at baseline and hourly following food intake for 8 h. Blood samples were analyzed for appetite hormones and SCFAs using radioimmunoassay and GC-MS. Ileal samples were analyzed for metabolic profiling using (1)H-NMR spectroscopy, partial least squares discriminant analysis with Monte-Carlo cross-validation and repeated-measures design. RESULTS: HFP but not HF had higher PYY levels than the LF (P = 0.004). BH and serum total SCFAs were higher in HF and HFP than LF indicating a higher bacterial fermentation (P = 0.021, 0.015 and P = 0.000, 0.003). HFP group had higher total SCFA than HF (P = 0.015). Distinct metabolic differences were identified in ileal samples from groups (e.g., time = 2 h, HF vs HFP R(2)Y: 0.99, Q(2)Y: 0.65). Ileal samples will be analysed for microbial profile (16 s rRNA, Illumina MiSeq), glucose and starch (spectroscopy) and SCFAs (GC-MS). CONCLUSIONS: Current data suggests a potential benefit of domestically processed food structures on appetite suppression as measured by postprandial PYY levels. This may be related to the different metabolic profiles generated in the ileum. Better understanding of this link can aid the design of diets that enhance appetite suppression and reduce food intake. FUNDING SOURCES: BBSRC.

OBJECTIVES: To measure basal metabolic rate (BMR) and to compare the values with estimated BMR from international and local predictive equations in inflammatory bowel disease (IBD) patients. METHODS: A total of 72 (38 women) subjects with Chron's disease (n = 45, 19 women) and ulcerative colitis (n = 27, 19 women) from an outpatient care unit in Rio de Janeiro, Brazil, agreed to participate in the study. Anthropometric measures were obtained using standard procedures. Percent body fat (PBF) was assessed by DXA. BMR was measured (BMR(m)) by indirect calorimetry (Vmax Encore 29) under standardized conditions and compared with BMR estimated by internationally-recommended (Schofield, 1985) and locally-developed (Anjos et al., 2014) predictive equations. Bias was calculated as estimated - measured BMR. RESULTS: The mean ± SD (range) age was 38.0 ± 11.3 (20.1 – 58.3) years with a mean BMI of 24.7 ± 4.5 (16.1 – 39.1) kg.m(−2) and PBF of 32.2 ± 9.1 (9.7 – 53.4). BMR(m) was significantly lower in women (1169.3 ± 205.0) than men (1439.0 ± 197.5) kcal.day(−1). The Schofield's equations significantly overestimated BMR for both women (bias of 204.0 ± 148.3 kcal.day(−1) or 17.4%) and men (306.7 ± 171.0 kcal.day(−1) or 21.3%). The locally-developed equation yielded nonsignificant estimates for both women (−5.8 ± 143.7 kcal.day(−1) or −0.5%) and men (−19.9 ± 165.5 kcal.day(−1) or −1.4%). CONCLUSIONS: The findings of the present study indicate that internationally-recommended BMR predictive equations are not accurate to estimate BMR in IBD patients in a tropical setting. As observed in samples of healthy adults from the same city, the locally-developed BMR equations yield unbiased and accurate estimates for IBD patients. FUNDING SOURCES: CNPq (310,461/2016–20) and FAPERJ (E-26/202.514/2018; E-26/203.068/2018; E-26/203.068/2017; E-26/202.520/2016; E-26/210.747/2016).

OBJECTIVES: High protein (HP) diets during short-term energy restriction (ER) attenuate energy-mediated reductions in muscle protein synthesis (MPS). MPS-adaptive responses to HP diets during prolonged ER are not well described. This study examined the effects of prolonged ER and HP on MPS and the synthesis rates of numerous individual muscle proteins. METHODS: Female 6-wk-old obese Zucker (lepr(fa+/fa+), n = 48) rats were randomized to one of four diet groups for 10 weeks: ad libitum-standard protein (AL-SP; 14% protein), AL-HP (35% protein), ER-SP, and ER-HP (both fed 60% of intake of AL-SP). At the start of week 10, D(2)O was administered by intraperitoneal injection and isotopic equilibrium was maintained daily by providing D(2)O in drinking water. Rats were euthanized after 1 week of labeling, and mixed-MPS (gastrocnemius), absolute mixed-MPS (mixed-MPS x muscle protein content), proteome dynamics, and protein half-lives [rate/d (k) = –ln(1-f)/d, where f is mixed-MPS and t is time in days; t1/2 (days) = ln(2)/k] were quantified. RESULTS: Mixed-MPS was not altered by energy status and protein intake. Gastrocnemius mass was lower (P

OBJECTIVES: To investigate differences in ad libitum energy intake when inpatient adults were exposed to diets with equal calories and protein but varied widely in the ratio of carbohydrate to fat. METHODS: 16 adults without diabetes were admitted to the Metabolic Clinical Research Unit in the NIH Clinical Center for four continuous weeks and were randomized to receive either a plant-based, low-fat (LF) diet or an animal-based, low-carbohydrate (LC) diet for two weeks, followed by the alternate diet for two weeks. The LF diet was ∼75% carbohydrate and ∼10% fat, whereas the LC was ∼10% carbohydrate and ∼75% fat. The LF diet had ∼4-fold more fiber and was ∼60% of the energy density of the LC diet. Both diets were matched for protein and the presented calories were double each subject's maintenance energy requirements, as calculated from their measured resting energy expenditure multiplied by 1.6. Participants received three daily meals, had continuous access to snacks, and were instructed to eat as much or as little as they wanted. Leftovers were weighed to determine food intake. ProNutra software was used to calculate energy and nutrient intake. RESULTS: The study enrolled 9 men and 7 women with an age (mean ± SE) of 29 ± 1.7 years and body mass index (BMI) of 27.5 ± 1.5. During exposure to the LF diet, participants consumed 726 ± 84 kcal/d less than during the LC diet (P

OBJECTIVES: Apple pomace (AP) is a byproduct of apple juice production and is a rich source of fiber. The goal of the present study was to determine the impact of adding AP to 100% apple juice (AJ) on the postprandial glycemic response compared to sugar matched AJ or whole apple fruit (WAF) in healthy human subjects. METHODS: Fifty-eight healthy subjects (aged 25 ± 3 years, BMI 22.9 ± 1.4 kg m(−2), mean ± SD) participated in a randomized, 3-arm, cross-over clinical trial to test the glycemic response to AJ, 235 g, AJ with 5 g fiber from AP added (APF, 235 g total beverage weight) or whole Red Delicious apple with skin (WAF, 230 g edible portion with skin). Fiber content of APF was matched to WAF and all study products were matched for available carbohydrates (AJ/APF/WAF, 24 g). Blood samples were collected to measure glucose and insulin concentrations at fasting (0 min) and multiple time points over 2 h after consuming study product. The primary end point was the difference in maximal glucose concentrations (C(max)) among study products. RESULTS: Results indicated that Cmax values were not significantly different between 3 products (AJ −121.2 ± 1.8 mg/dL vs. APF- 120.8 ± 1.8 mg dL-1 vs. WAF 121.3 ± 1.8 mg dL-1, respectively, P > 0.05). Time to reach maximal glucose concentration (T max) was delayed in APF compared to AJ and WAF (33.2 ± 0.8 min vs. 29.9 ± 0.8 and 29.6 ± 0.8, respectively, P 0.05. CONCLUSIONS: This study demonstrated that adding 5 g of fiber from AP into 235 g of AJ did not attenuate maximal postprandial glucose concentration. However, times to reach maximal glucose and insulin concentrations were significantly delayed in the group receiving pomace fiber added to apple juice compared to apple juice alone or whole apple fruit. FUNDING SOURCES: Financial support for this study was provided by PepsiCo, Inc. The views expressed in this abstract are those of the authors and do not necessarily reflect the position or policy of PepsiCo, Inc.

OBJECTIVES: To assess different methods of estimating energy balance (EB) and its components in a sample of older people (age ≥ 60 years) living in a tropical city in Brazil. METHODS: EB was calculated in 85 older individuals (69 women) as the difference between energy intake (EI), obtained by three 24-hour dietary recalls on nonconsecutive days, and total daily energy expenditure (TDEE) estimated by 24-hour physical activity recalls (24hPAR, subjective method) and accelerometry (ACC, objective method) on the same days. Basal metabolic rate (BMR) was estimated by a validated local predictive equations derived from a sample of healthy adults from the same city and by international equations (Schofield). Resting energy expenditure (MET) was also estimated by local predictive equation and the conventional value of 3.5 mL.kg(−1).min(−1). Anthropometry and % body fat (DXA) assessment was also obtained. RESULTS: Mean (SD) age was 69.0 (5.5) years with a mean BMI of 26.7 (4.4) kg.m(−2) and %BF of 39.4 (7.9). BMR from locally-derived equations (1050.7 ± 188.7 kcal.day(−1)) was significantly lower than BMR estimated by the Schofield's equation (1286.5 ± 145.3 kcal.day(−1)). Likewise, predicted MET was significantly lower than the conventional value. Despite the high prevalence of overweight (66% with BMI ≥ 25 kg.m(−2)), EB was always negative for the 24hPAR method (−863.5 ± 799.5 kcal.day(−1)) but positive (252.1 ± 726.6 kcal.day(−1)) with the ACC method when MET was calculated with population-specific equations. EB estimated by ACC was also negative (−122.7 ± 781.0 kcal.day(−1)) using the conventional MET value. CONCLUSIONS: The findings of this study indicate that EB is negative when the subjective method of TDEE estimation is used but becomes positive with the objective method. It is also evident that BMR and MET equations derived from samples of the population of interest may help improve the final estimates of TDEE and EB in older adults. FUNDING SOURCES: CNPq (310,461/2016–20 and 485,168/2011–1) and FAPERJ (E-26/111.496/2011; E-26/202.514/2018; E-26/203.068/2017).

OBJECTIVES: Polycystic Ovarian Syndrome (PCOS) is the most common female endocrine disorder and a leading cause of female infertility in the US. In addition, PCOS women have an increased risk of developing type 2 diabetes (T2DM), hypertension (HTN) and heart disease. One of the most significant factors associated with HTN is increased circulating angiotensin II (Ang II). Metabolites generated as result of whey protein digestion improve insulin sensitivity, inhibit ACE (an enzyme responsible for production of Ang II) thereby playing an important role in the prevention of HTN and associated cardio-vascular pathologies. These benefits of whey protein ingestion have been demonstrated in normal populations and in individuals with T2DM.The purpose of this study was to examine changes in blood pressure (BP), Ang II and Adiponectin concentrations following 40 days of whey protein supplementation and to examine differences in baseline measurements of between body fat distribution in PCOS women and healthy controls (CON). METHODS: Women with PCOS and CON consumed 35 g of whey protein for 40 days. Baseline, Day 20 and Day 40 concentrations were measured via plasma and serum collection. Resting BP (Systolic and Diastolic pressures; SBP and DBP respectively) were measured with an electronic monitor were used to calculate mean arterial pressure (MAP) at baseline, Day 20 and Day 40. DXA was used to estimate body composition and fat distribution (total body fat, trunk fat and Android: Gynoid fat ratio [A: G]) at baseline. RESULTS: Preliminary analyses indicates that at baseline SBP was significantly lower in the CON group compared to PCOS. However, DBP and MAP had no significant differences at baseline. The PCOS group also had lower adiponectin levels at baseline when compared to the CON group. Ang II concentrations, as well as Day 20 and Day 40 analysis are currently being evaluated. CONCLUSIONS: Overall, our results indicate that vascular health is compromised in young women with PCOS compared to health controls. Results from this research, will not only help provide a better understanding of the link between inflammatory markers such as Ang II and the increased risk of HTN commonly seen in women with PCOS, but it also provide a nutritional intervention to help prevent these disorders. FUNDING SOURCES: Glanbia Nutritionals, Inc., TWU Research Enhancement Program, TWU Human Nutrition Research funds.

OBJECTIVES: Branched-chain amino acids (BCAAs) are essential amino acids that are crucial for skeletal muscle anabolism. Thus, alterations in their levels are associated with muscle atrophic diseases such as cancer, chronic inflammatory and neurological disorders. Others have linked impairments in BCAA metabolism to the development of insulin resistance and its sequelae. Compared to the effects of theses amino acids, much less is known on how impairment in BCAA catabolism affects skeletal muscle. BCAA catabolism starts with the reversible transamination by the mitochondrial enzyme branched-chain aminotransferase 2 (BCAT2). This is followed by the irreversible carboxylation, catalyzed by branched-chain ketoacid dehydrogenase (BCKD) complex. We have shown that BCAT2 and BCKD are essential for the differentiation of skeletal myoblasts into myotubes. Here, we investigated the effect of depletion of BCAT2 or of E1a subunit of BCKD in differentiated myotubes. METHODS: On day 4 of differentiation, L6 myotubes were transfected with the following siRNA oligonucleotides: scrambled (control), BCAT2, or E1a subunit of BCKD. RESULTS: Forty-eight hours after transfection, compared to control or BCAT2 siRNA group, we observed improved myotube structure in BCKD-depleted cells. BCKD depletion augmented myofibrillar protein levels: myosin heavy chain (MHC, 2-fold) and tropomyosin (4-fold), P

OBJECTIVES: Tracking food and beverage intakes daily on a modified Ketogenic diet (MKD) pattern is time consuming, challenging and often, incomplete. The objective of this pre-post test design study was to examine different measures of nutritional ketosis in relation to reported dietary intakes before and during the adoption of the MKD for 8 days. METHODS: A sample of 19 adult women (mostly nutrition professionals) were instructed on a MKD, monitored foods and beverages consumed daily using the Carb Manager(©) app (Wombat Apps LLC, WA) and checked urinary ketones (Siemens Labstix Reagent Strips (Malvern, PA, USA)) each morning. On days 0, 7 and 8, participants fasted overnight and provided urine and capillary blood samples for determination of urinary acetoacetate (AoAc) and beta-hydroxybutyrate (BHB) concentrations, respectively. BHB concentrations were determined with device A, Precision Xtra (Alameda, CA, USA) and; device B, KetoMojo (Napa, CA, USA). Nutritional ketosis was defined as blood BHB ≥ 0.5 mmol/L or urinary AoAc ≥ 15 mg/dL. Descriptive statistics and correlations were run using SPSS version 23 (IBM Corp, 2015). RESULTS: At baseline, two-day averages of net carbohydrate (nCHO), energy, fiber, protein, and fat were as follows (median, (IQR)): 106 (81, 137); 1470 (1194, 1689); 11.8 (8.0,19.0); 64.2 (47.4, 80.6); and 67 (48, 78). All components except for energy are reported as grams/day. Baseline urinary AoAc concentrations were non-detectable; blood BHB by device A were 0.1 (0.1, 0.2) while device B were 0.1 (0.1, 0.1) mmol/L. Once on the MKD for 7 and 8 days, two-day averages of net carbohydrate (nCHO), energy, fiber, protein, and fat were as follows (median, (IQR)): 27 (25, 30); 1527 (1346, 1638); 18.2 (12.0, 22.2); 64.0 (49.9, 72.2); and 111 (95, 137). Day 8 urinary AoAc levels were 15 (5, 80) mg/dL while blood BHB were 0.6 (0.4, 1.3) with device A and 0.8 (0.3, 1.8) mmol/L with device B. Changes in nCHO intake were correlated with Day 8 BHB values (device A, rho = −0.655, P = 0.004 and device B, rho = −0.652, P = 0.005), and with urinary AoAc (rho = –0.631, P = 0.007). CONCLUSIONS: All ketone biomarkers reflected changes in nCHO intake. Further study is warranted to confirm these observations and provide estimates of biomarker reliability to determine the most cost-effective method for assessing adherence to the MKD. FUNDING SOURCES: Departmental.

OBJECTIVES: Gestational Diabetes Mellitus (GDM) is present in up to 10% of pregnancies in the United States. The occurrence of GDM causes severe short- and long-term complications for the mother and offspring. baby pre- and post-partum. Identification of the metabolites and potential biomarkers involved in GDM could improve the prediction of its occurence. The integration of food data with metabolite results could provide innovative diet intervention strategies. The objective of this study is to identify metabolites that differed in the first and third trimesters of GDM versus Non-GDM pregnancies. METHODS: Participants were 68 OW/OB pregnant women enrolled in the Healthy Beginnings Trial and completed blood draws at first (10–16 weeks) and third trimester (28–35 weeks). Participants from the control and dietary intervention group who developed GDM (n = 34; GDM group) were matched on age, BMI, ethnicity, and treatment group with those who did not develop GDM (n = 34; Non-GDM group). Plasma samples were analyzed by ultra-high-performance liquid chromatography-hybrid triple‐quadrupole linear ion trap mass spectrometry (UPLC-QTRAP) using three targeted metabolomics assays for primary metabolomics, aminomics and lipdomics. Dietary intake was estimated using 24 hour recalls in order to assess potential dietary differences between groups. RESULTS: A total of 243 metabolites were identified in the plasma samples. At first trimester, several complex lipids, including cholestryl esters and phospholipids, were higher in the GDM group (P

OBJECTIVES: The objective was to 1) determine if carbonation, flavor, and sweetness in beverages impact blood glucose response after consumption and 2) to determine if there is a relationship between fasting glucose concentrations, acylated ghrelin, and blood lipid concentrations. METHODS: Participants (males n = 11, females n = 14) aged 23–65, BMI 0.05). The average blood glucose concentration among beverage and time points was 96.68 + 7.76 mg/dL (mean ± SD). There was no correlation between fasting blood glucose (0 min), acylated ghrelin, or any blood lipid measurements (P > 0.05). There was a correlation between LDL and total cholesterol concentrations (r = .780, P =

OBJECTIVES: Obesogenic, high fat diets (HFD) increase hepatic long chain polyunsaturated fatty acid content (LCPUFA), but also lead to hepatic steatosis and insulin resistance. Fermentable fiber such as inulin (INU) may reduce these negative outcomes via a bile acid (BA)-liver signaling axis. This study tests the hypothesis that INU maintains elevated LCPUFA but reduces HFD-induced insulin resistance and fatty liver and investigates the potential relationship of bile acids. METHODS: Male mice (4 wk) were fed a low fat diet (LFD) (16% en fat) or HFD (48% en fat) containing 10% non-fermentable cellulose (CL) or 3% CL and 7% INU for 13 wks in a 2 × 2 factorial design. Tissue, plasma, and cecal contents were collected week 13. RESULTS: Intake of the HFD-CL increased hepatic LCPUFA content and steatosis and reduced insulin sensitivity vs LFD treatments. INU maintained HFD-induced LCPUFA elevation, improved insulin sensitivity, due to reductions in fasting glucose, but did not mitigate HFD-induced hepatic steatosis. When standardized to the hepatic triacylglycerol (TAG) content, LCPUFA (notably 22:6n-3) were increased by INU in the LFD only. The BAs with highest cecal concentrations were deoxycholic (DCA) and beta/omega murine cholic (B/OMCA) acids. INU increased cecal wt and decreased concentrations of DCA and B/OMCA. INU-induced B/OMCA reductions were enhanced by the HFD, but the DCA effects were independent of % en fat. The expression of multiple lipid metabolic genes was assessed. Of these, reductions in Scd1 expression occurred with both HFD and INU treatments compared to LFD-CL. SREBP1c, Fasn, Scd1, Elov5, Fads1, and Fads2 correlated with murine cholic acids and cholic acid in HFD-INU but only weakly in LFD-INU. These relationships were not evident with the CL-based diets. CONCLUSIONS: INU in an HFD provided mixed outcomes by maintaining elevated hepatic LCPUFA, reducing fasting plasma glucose concentrations but failing to reduce fasting insulin concentrations and hepatic steatosis. While cecal BAs and hepatic gene expression correlated with the INU treatments, these mechanistic changes did not mitigate HFD-induced hepatic steatosis. FUNDING SOURCES: USDA-ARS.

OBJECTIVES: Free fructose but not total fructose intake could contribute to the formation of advanced glycation end products (AGEs) and Maillard reaction products in the intestinal lumen. Therefore, the aim of this study was to compare serum levels of fructosamine, soluble receptor for AGEs (sRAGE), and urinary levels of glyoxal and methylglyoxal after free fructose and total fructose intake. METHODS: This is a randomized crossover study, approved by the Institutional Committee of Bioethics in Research of the University of Guanajuato (CIBIUG). Twelve clinically healthy subjects, 20–30 years old, were recruited. During the first visit, participants were randomly assigned to one of two treatments, an oral load of fructose (40 g) or total fructose (40 g fructose and 40 g glucose), in addition to their assigned treatment subjects received 25 g of hydrolyzed protein (Nature Best Isopure®) After a washing period (one week), participants were crossed over to receive the other treatment. Blood and urine samples were collected at baseline and after three hours of the oral load of each treatment. Glucose, creatinine, and lipids serum levels were measured with commercial kits. Insulin, fructosamine, and sRAGE serum levels were determined with ELISA commercial kits. Glyoxal and methylglyoxal urine levels were quantified by HPLC. Data analysis was completed using STATISTICA 10 and IBM SPSS Statistics 24.0 software. The results were considered significant with a value of P

OBJECTIVES: We reported that healthy males supplemented with testosterone gained lean body mass (LBM) during 28-d of energy deficit and 14 d of ad libitium feeding when measured by dual energy x-ray absorptiometry (DXA), but with no increase in muscle strength. We were unable to determine whether LBM gains were due to muscle mass accrual since DXA does not deliniate muscle from visceral organs and body water. Objectives: To assess the effects of testosterone supplementation on muscle mass as measured by creatine (methyl-d(3)) dilution, and determine the relationship between muscle mass and DXA-measured LBM in response to short-term energy deficit. METHODS: Secondary analysis of a 3-phase, randomised, double-blind, placebocontrolled trial in healthy males: 14-d free-living, eucaloric phase (P1); 28-d live-in, 55% energy deficit phase with (200 mg testosterone enanthate/wk, TEST, n = 24) or without (PLA, n = 26) testosterone (P2); and 14-d free-living, ad libitum feeding phase (P3). Muscle mass was measured by creatine dilution and LBM by DXA at the end of each phase. RESULTS: We previously reported increased LBM in TEST (mean change from P1 ± SEM; 2.5 ± 0.4, P 0.05), following P2. Both TEST (5.2 ± 0.4 kg) and PLA (2.2 ± 0.4 kg) gained LBM in P3 (P 0.05). Cross-sectional measures of muscle mass were correlated (P 0.05). CONCLUSIONS: Testosterone supplementation increased LBM in response to short-term energy deficit and recovery feeding, but had no significant effect on muscle mass or muscle function. The discordance between changes in LBM and muscle mass underscore the inherent limitations of LBM as a surrogate measure for skeletal muscle mass, particularly in response to short-term intervention studies. FUNDING SOURCES: DHP JPC-5/MOMRP; authors’ views not official U.S. Army or DoD policy.

OBJECTIVES: The purpose of this study was to examine the acute effects of consuming isocaloric, higher-protein breakfast shakes varying in protein source on satiety-stimulating hormone PYY concentrations in healthy adults. METHODS: Thirty-two adults (Age: 25 ± 1y; BMI: 24.2 ± 0.5 kg/m(2)) randomly consumed 250 kcal higher-protein breakfast shakes (24 g total protein; 17 g CHO; 9 g fat), varying only in protein source (whey protein isolate, WHEY; soy protein isolate, SOY; Micellar Casein, CAS; pea protein isolate, PEA; and milk protein isolate; MILK) for 3 days/shake. On day 4, the participants completed a 4-h testing day that included the consumption of the respective shake followed by blood sampling collected every 30 min to assess plasma Total PYY concentrations. Area under the curve (AUC) analyses were performed. RESULTS: Regardless of protein source, the consumption of a breakfast shake led to increases in postprandial PYY concentrations throughout the 4-h period. Although no differences in total (4-h) PYY AUC responses were detected between treatments, PEA elicited greater increases in PYY concentrations during the first 2 postprandial hours compared to MILK and CAS (both, P

OBJECTIVES: Results from observational studies indicate that whole grain intake is inversely associated with BMI and risk of weight gain. Whole grain intake may influence energy balance and body composition through effects on appetite and thus, energy intake. To evaluate the impact of whole grain food consumption on appetite, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing whole grain food intake and subjective measures of appetite in adults. METHODS: A search of PubMed, Scopus and Food Science and Technology abstracts yielded 34 RCTs measuring hunger ratings after consuming whole grain foods compared to refined grain controls. Seventeen of these studies (598 subjects), with a total of 33 unique whole grain treatments, reported areas under the curve (AUC) for subjective hunger and were included in the meta-analysis. Pooled estimates from meta-analyses are expressed as standardized mean differences (SMD). RESULTS: Intake of whole grain foods resulted in significantly lower subjective hunger AUC (range for AUC times ranged from 120 to 270 min) compared to refined grain foods [SMD −0.36, P

OBJECTIVES: The FDA after approximately 25-plus years of deliberations approved the definitions of dietary fiber (DF). Concurrently with these definitions, the FDA has approved 16 sources of Added Fiber (AF) to DF status, thus allowing their inclusion as DF in foods and on the Food Label. While the Institute of Medicine defined DF as the nondigestible carbohydrates (NDC) mainly in plant foods, they also used the term Added Fiber (AF) for any NDC extracted from a food or synthesized. The 16 sources of AF were approved for their clinical ability to demonstrate a “beneficial physiological effect for human health” (BPEFHH). The objective of this report is to give the range and mean value in grams, reported respectively, after each named AF to achieve a BPEFHH. METHODS: The method used to obtain this information was to review the major references used by the FDA is making their decisions. RESULTS: The results of the FDA approvals are: b-glucan (3 g/day) and psyllium husk (7 g/day} were reaffirmed as DF having previously been granted health claims to lower cholesterol. Other sources of AF approved to attenuate blood cholesterol levels were guar gum (15–30; 20), pectin (9–36; 17), locus bean gum (8–24; 17) and hydroxypropylmethylcellulose (5–15;9). The FDA approved, “mixed plant cell wall fibers” (intrinsic and intact)” as an encompassing term incorporating many of the AF individually approved. Arabinoxyln (2.6–15; 8), alginate (1.5–15; 9), and the resistant starches, RS-2 (25–40; 32) and RS-4 (17;17-one study) were approved for their ability to attenuate blood glucose and or insulin levels. Inulin and inulin-type fructans (3–44; 8), galactooligosaccharide (5–20; 11), and resistant maltodextrin were approved having demonstrated enhanced calcium absorption and or bone calcium retention. Polydextrose ((6.25; 13) was approved for its ability to reduce food (calorie) intakes thus helping to reduce body weight, promote satiety while only providing one (1) kcal/g. CONCLUSIONS: In the FDA approval declarations, they commented they will “consider enforcement discretion for declaring the amount of [AF]” as DF to demonstrate BPEFHH. But for the time being, these FDA approvals explain the BPEFHH of AF and help justify the need for more DF in the diet. FUNDING SOURCES: None.

OBJECTIVES: In mice, low protein (LP) diets increase food intake (FI) thereby energy intake, to compensate for protein deficiency, but mice do not gain fat because total energy expenditure (TEE) is also increased. Fibroblast Growth Factor 21 (FGF21), which is expressed in the liver and in the brain, appears as a key player in these effects. The present study hypothesized that both LP diet but also only lysine or threonine deficiency can modulate FGF21 in the liver and in the hypothalamus that in turn is involved in the control of FI and energy expenditure. METHODS: Growing rats were fed for 3 weeks: i) LP diets containing 3-5-8-12-15 or 20% of milk protein, or ii) the same diets but supplemented with free amino acids at the level of the 20% protein diet except for lysine or threonine leading to lysine or threonine deficient diets. Body weight and FI were measured daily and energy expenditure were measured by indirect calorimetry. At the end of the experiment, rats were euthanized, tissues and biological fluids were removed and frozen, and body composition as well as gene expression and plasma FGF21 were analyzed. RESULTS: Diets with 3 and 5% protein, and diets highly deficient in lysine or threonine (85% and 75%) result in significant growth retardation. LP 3% and 5% induced an increase in relative FI. Surprisingly, an increase in TEE was observed under LP 5% protein, due to an increase in motor activity. Hepatic FGF21 expression is increased at 3 and 5% and strongly decreased at 12, 15 and 20% protein. In contrast, in the hypothalamus, FGF21 expression was significantly lower in LP 3% compared to a 20% protein diet, and for the other LP diets, the values are intermediate. Plasma FGF21 was higher in 3, 5, 8 and 12% protein than in 15 and 20% protein diets. Lysine or threonine deficiency were able to reproduce the effect of LP diet at 3 and 5% whereas at 8%, only the deficiency of threonine was able to reproduce the LP effect. CONCLUSIONS: These results showed that hepatic and hypothalamic expression FGF21 are inversely affected by protein deficiency. Such situations of deficiency induced an up-regulation of hepatic expression of FGF21 that increased TEE and a down-regulation of hypothalamic expression of FGF21 that could led to hyperphagia. Interestingly, the levels of FGF21 observed for the 3, 5, 8% protein diets could be due at least to lysine and threonine deficiency. FUNDING SOURCES: ABIES, AlimH department of INRAe.

OBJECTIVES: Many persons with an HIV infection and undergoing treatment with Highly Active Anti-Retroviral Therapy (HAART) still experience weight loss, hyperglycemia, hyperlipidemia, gastrointestinal issues (diarrhea and malabsorption), and ectopic fat-redistribution typical of acquired lipodystrophy. Symptoms include non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. This study aimed to further elucidate the relationship between malabsorption in HIV infected males, the macronutrient content of feces, and the association with anthropometric measurements and NAFLD and liver fibrosis. METHODS: This research enrolled fourteen male participants that are HIV infected, and 14 non-infected males that were matched for age and body mass index (BMI). Anthropometric measurements BMI and hip to waist ratio were obtained, along with a liver scan for fatty liver and fibrosis using the ARFI ultrasound technique. A full bowel movement was collected for each participant, a small aliquot was collected for future microbiome analysis and the remainder was freeze-dried and stored at −80 C. Proximate analysis of feces were completed for macronutrient composition. Analyses included bomb calorimetry for total kilocalories, kjeldahl and soxhlet for % crude protein and crude fat, respectively, and fiber analysis for % insoluble, soluble, and total fiber. RESULTS: There were no significant differences found between groups in macronutrient content of the feces. Differences between insoluble and soluble fiber approached statistical significance between groups, with HIV infected males having a greater proportion with P = 0.080, and 0.072 respectively. Anthropometric data approached statistical significance, with the HIV infected males exhibiting a greater value for liver damage (P = 0.060) and hip to waist ratio (P = 0.015). CONCLUSIONS: Surprisingly, macronutrients differences, especially soxhlet (fat level in feces) and bomb calorimetry (total kcals for fecal dry matter) were similar between HIV and non-infected controls even though HIV participants reported GI symptoms. Future analysis of the microbiome may identify altered community metabolism that could result in GI symptoms despite no evidence from macronutrient analysis. FUNDING SOURCES: Seed Grant, Center of Excellence in Inflammation, Infectious Diseases and Immunity, ETSU.

OBJECTIVES: To determine the level of accuracy of recommended resting metabolic rate (RMR) prediction equations among healthy and acutely ill males: aged 18 to 65-years, in Trinidad and Tobago. METHODS: Following informed consent and enrolment, sixty-six male (acutely ill 33; healthy 33) volunteers had anthropometry and RMR (MedGem® indirect calorimeter, Micro life, USA) measured using recommended procedures. RMR from prediction equations were compared to RMR measured by indirect calorimetry with values between ±10% of measured RMR being considered accurate. The university's ethics committee approved the study. RESULTS: The top-four ranked recommended RMR prediction equations for acutely ill males, in decreasing order of accuracy were Müller (39.4%), Bernstein (39.4%), Korth (36.4%) and Mifflin St. Joer (36.4%). Among the healthy males, the top-five ranked recommended RMR prediction equations were Müller (54.5%), Huang (54.5%), Lürhmann (51.5%), Korth (48.5%) and Valencia (48.5). Population-derived RMR prediction equations had 54.5% and 63.6% accuracies among the acutely ill and healthy males respectively. These were significantly higher than the top-ranked recommended prediction equations for both groups. Notably, limiting the risk of malnutrition by at least 5%: through diet quality by way of accurate energy predictions could improve health-related quality of life. Increasing the predictability of energy needs within any population can also ensure the accuracy of RMR per weight (kilogram) needed daily and energy balance. On average, this male population utilized 17.5 kcal of energy per kilogram body weight. CONCLUSIONS: All other recommended RMR prediction equations except Huang, Lürhmann, and Müller resulted in biases >50%. Substituting the commonly used prediction equations with our population-specific equation can increase the level of accuracy by at least 10%, thus limiting the risk of malnutrition by at least 5%, and improving health-related quality of life for this male population. FUNDING SOURCES: nil.

OBJECTIVES: The efficacy of oat beta-glucan (OBG), a viscous soluble fibre, on postprandial glycemic outcomes may depend on the nature of the control and the dose and molecular weight (MW) utilized. We undertook a systematic review and meta-analysis of acute clinical trials to determine whether these features mediate the glycemic response to OBG. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through October 2, 2019. We included acute, single-meal feeding, controlled trials investigating the effect of OBG (concentrate or oat bran) added to a carbohydrate-containing meal compared to a comparable meal (matched control) or a different carbohydrate-containing meal (unmatched control). Two reviewers extracted the data and assessed the risk of bias. The primary outcome was incremental area under the curve (iAUC) for blood glucose. Data were pooled using the generic-inverse variance method with random effects model and expressed as ratio of means with [95% Cis]. RESULTS: We included 93 trial comparisons (N = 432). OBG reduced glucose iAUC by 23% (0.77 [0.73 to 0.81]). The effect was not significantly different between matched and unmatched controls (P = 0.17). Dose and MW were significant effect modifiers (P 5.5 g OBG led to reductions of 9% (0.91 [0.81 to 1.02]), 14% (0.86 [0.80 to 0.93]), 17% (0.83 [0.76 to 0.90]), 31% (0.69 [0.64 to 0.74)], and 39% (0.61 [0.56 to 0.66]), respectively. Low MW OBG (1000,000 g/mol) OBG led to significant reductions of 23% (0.77 [0.69 to 0.87]) and 32% (0.68 [0.63 to 0.73]), respectively. CONCLUSIONS: Current evidence indicates that the addition of oat beta-glucan to carbohydrate-containing meals reduces the postprandial glycemic response. However, the magnitude of the reduction depends on the dose and the molecular weight of the oat beta-glucan. FUNDING SOURCES: INQUIS Clinical Research Ltd. (formerly GI Labs), and PepsiCo Global R&D.

OBJECTIVES: The muscle protein synthetic response to the ingestion of animal based proteins has been reported to be superior to the ingestion of plant based proteins. The lesser anabolic properties of plant based compared with animal based proteins has been attributed to differences in essential amino acid (EAA) contents and amino acid composition. This study compares post-prandial muscle protein synthesis rates following the ingestion of 30 g milk protein with the ingestion of 30 g corn protein or a blend of 30 g corn and milk protein in vivo, in young males. METHODS: In a randomized, double blind, parallel-group design, 36 healthy young males (26 ± 4 y) received a primed continuous infusion of L-[ring-(13)C(6)]-phenylalanine and ingested 30 g milk protein (MILK), 30 g corn protein (CORN), or a blend of 15 g corn protein plus 15 g milk protein (CORN + MILK) (n = 12 per group). Blood and muscle biopsies were collected for 5 h following protein ingestion to assess post-prandial plasma amino acid profiles and myofibrillar protein synthesis rates. Data were analyzed with 2-way repeated measures ANOVA and independent samples t-test. Data are expressed as mean ± SD. RESULTS: MILK increased plasma EAA concentrations more when compared to CORN (incremental area under curve (iAUC): 151 ± 31 vs 77 ± 19 mmol/L/300 min, respectively; P

OBJECTIVES: Fibroblast Growth Factor 21 (FGF21), a response to metabolic stress, is influenced by the dietary protein content. Previous studies have shown that a protein level below 10% of energy increases FGF21 hepatic secretion in mice, and increases food intake and energy expenditure. However, it has also been shown in vitro that glucose stimulates FGF21 secretion in liver. The objective of this study was to determine the respective roles of dietary protein and carbohydrate contents on FGF21 secretion and associated metabolic responses. METHODS: 70 male Wistar rats were subjected at one to 12 diets with various milk protein contents (3, 5, 8, 15 and 30% P of energy) and a mixture of carbohydrates and fats in which carbohydrates amounted 30, 45, 60 or 75% of energy. Body weight and energy intake were measured twice a week, and energy expenditure was measured one time after 2 weeks by indirect calorimetry. After 3 weeks, plasma was collected and an ELISA test was used to determine plasma concentration of FGF21. Tissues were dissected and weighed to determine body composition. Pieces of liver were frozen for measuring expression of Fgf21 mRNA by RT-PCR. Statistical analyzes were done by analysis of variance. RESULTS: The decrease in %P in diets increased liver Fgf21 mRNA. Using the 30% P fed group as a reference, Fgf21 mRNA were increased not significantly 3x in 15% P, but significantly 19x in 8% P, 44x in 5% P and 60x in 3% P (P