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Male breast cancer, while uncommon, is a highly malignant disease. Monocyte chemotactic protein-1 (MCP-1) is an adipokine; its concentration in adipose tissue is elevated in obesity. This study tested the hypothesis that adipose-derived MCP-1 contributes to male breast cancer. In a 2x2 design, male MMTV-PyMT mice with or without adipose-specific Mcp-1 knockout [designated as Mcp-1-/- or wild-type (WT)] were fed the AIN93G standard diet or a high-fat diet (HFD) for 25 weeks. Mcp-1-/- mice had lower adipose Mcp-1 expression than WT mice. Adipose Mcp-1 deficiency reduced plasma concentrations of MCP-1 in mice fed the HFD compared to their WT counterparts. Mcp-1-/- mice had a longer tumor latency (25.2 weeks vs. 18.0 weeks) and lower tumor incidence (19% vs. 56%), tumor progression (2317% vs. 4792%), and tumor weight (0.23 g vs. 0.64 g) than WT mice. Plasma metabolomics analysis identified 56 metabolites that differed among the four dietary groups, including 22 differed between Mcp-1-/- and WT mice. Pathway and network analyses along with discriminant analysis showed that pathways of amino acid and carbohydrate metabolisms are the most disturbed in MMTV-PyMT mice. In conclusion, adipose-derived MCP-1 contributes to mammary tumorigenesis in male MMTV-PyMT. The potential involvement of adipose-derived MCP-1 in metabolomics warrants further investigation on its role in causal relationships between cancer metabolism and mammary tumorigenesis in this male MMTV-PyMT model.

Structural differences in dietary fatty acids modify their rate of oxidation and effect on satiety, endpoints that may influence the development of obesity. This study tests the hypothesis that meals containing fat sources with elevated unsaturated fats will result in greater postprandial energy expenditure, fat oxidation, and satiety than meals containing fats with greater saturation. In a randomized, 5-way crossover design, healthy men and women (n = 23, age: 25.7 ± 6.6 years, BMI: 27.7 ± 3.8 kg/m2) consumed liquid meals containing 30 g of fat from heavy cream (HC), olive oil (OO), sunflower oil (SFO), flaxseed oil (FSO), and fish oil (FO). Energy expenditure and diet-induced thermogenesis (DIT) were determined by metabolic rate over a 240 min postprandial period. Serum concentrations of ghrelin, glucose, insulin, and triacylglycerol (TAG) were assessed. DIT induced by SFO was 5% lower than HC and FO (p = 0.04). Energy expenditure and substrate oxidation did not differ between fat sources. Postprandial TAG concentrations were significantly affected by fat source (p = 0.0001). Varying fat sources by the degree of saturation and PUFA type modified DIT but not satiety responses in normal to obese adult men and women.

OBJECTIVES: A Mediterranean diet (Med Diet) decreases atherogenic lipoproteins and cardiovascular disease (CVD) risk. It is unknown how high cholesterol intake within a Med Diet will affect these parameters. The objective of this project was to evaluate the daily inclusion of whole eggs, a high cholesterol food, in the Med Diet on lipid and lipoprotein profiles. METHODS: Overweight to obese men (8) and women (25) were recruited into a randomized, cross-over designed, controlled feeding study evaluating three isocaloric test diets: a) Control –average American diet from What We Eat in America, b) Med Diet, and c) Med Diet plus whole, fresh eggs (1 whole egg/1000 kcal; Med Diet + Egg). The Control and Med Diet contained egg substitute. Participants were directed to consume only those foods provided during each 4-week diet treatment period. Each treatment period was separated by > 4-week washout period. Fasting blood was taken pre- and post-treatment for determination of lipid concentrations, lipoprotein particle size and number. RESULTS: Intake of the Control and Med Diet, but not the Med Diet + Egg, decreased (time effect, P

Background Supplementation with long chain n‐3 polyunsaturated fatty acids is used to reduce total circulating triacylglycerol (TAG) concentrations. However, in about 30% of people, supplementation with long chain n‐3 polyunsaturated fatty acids does not result in decreased plasma TAG. Lipidomic analysis may provide insight into this inter‐individual variability. Methods Lipidomic analyses using targeted, mass spectrometry were performed on plasma samples obtained from a clinical study in which participants were supplemented with 3 g/day of long chain n‐3 in the form of fish oil capsules over a 6‐week period. TAG species and cholesteryl esters (CE) were quantified for 130 participants pre‐ and post‐supplementation. Participants were segregated into 3 potential responder phenotypes: (1) positive responder (R pos ; TAG decrease), (2) non‐responder (R non ; lacking TAG change), and (3) negative responder (R neg ; TAG increase) representing 67%, 18%, and 15% of the study participants, respectively. Separation of the 3 phenotypes was attributed to differential responses in TAG with 50 to 54 carbons with 1 to 4 desaturations. Elevated TAG with higher carbon number and desaturation were common to all phenotypes following supplementation. Using the TAG responder phenotype for grouping, decreases in total CE and specific CE occurred in the R pos phenotype versus the R neg phenotype with intermediate responses in the R non phenotype. CE 20:5, containing eicosapentaenoic acid (20:5n‐3), was elevated in all phenotypes. A classifier combining lipidomic and genomic features was built to discriminate triacylglycerol response phenotypes and reached a high predictive performance with a balanced accuracy of 75%. Conclusions These data identify lipidomic signatures, TAG and CE, associated with long chain n‐3 response p henotypes and identify a novel phenotype based upon CE changes. Registration URL: https://www.ClinicalTrials.gov ; Unique Identifier: NCT01343342.

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.

Background/aim Time restricted feeding (TRF) mitigates the high-fat diet-enhanced mammary tumorigenesis in a MMTV-PyMT breast cancer model. Materials and methods We performed untargeted metabolomic and targeted transcriptomic analyses on mammary tumors from MMTV-PyMT mice fed a standard AIN93G diet, a high-fat diet (HFD), or HFD with TRF (12 h, dark phase) and mammary glands from wild-type mice fed the AIN93G diet. Results The metabolic profile of mammary tumors differed from that of mammary glands; there was no impact of TRF upon tumor metabolome. TRF did reduce elevated expression of Hmgcr, Srebp1, Fads2, and Ppard in mammary tumors, indicating a down-regulation of lipid metabolism. Conclusion The null effect of TRF on the metabolomic profile does not rule out changes in more refined intracellular signaling pathways. It suggests that the protection of TRF against mammary tumorigenesis may rely upon its action on the host rather than a direct effect on tumor metabolism.

Time-restricted feeding (TRF) can reduce adiposity and lessen the co-morbidities of obesity. Mice consuming obesogenic high-fat (HF) diets develop insulin resistance and hepatic steatosis, but have elevated indices of long-chain polyunsaturated fatty acids (LCPUFA) that may be beneficial. While TRF impacts lipid metabolism, scant data exist regarding the impact of TRF upon lipidomic composition of tissues. We (1) tested the hypothesis that TRF of a HF diet elevates LCPUFA indices while preventing insulin resistance and hepatic steatosis and (2) determined the impact of TRF upon the lipidome in plasma, liver, and adipose tissue. For 12 weeks, male, adult mice were fed a control diet ad libitum, a HF diet ad libitum (HF-AL), or a HF diet with TRF, 12 hours during the dark phase (HF-TRF). HF-TRF prevented insulin resistance and hepatic steatosis resulting from by HF-AL treatment. TRF-blocked plasma increases in LCPUFA induced by HF-AL treatment but elevated concentrations of triacylglycerols and non-esterified saturated fatty acids. Analysis of the hepatic lipidome demonstrated that TRF did not elevate LCPUFA while reducing steatosis. However, TRF created (1) a separate hepatic lipid signature for triacylglycerols, phosphatidylcholine, and phosphatidylethanolamine species and (2) modified gene and protein expression consistent with reduced fatty acid synthesis and restoration of diurnal gene signaling. TRF increased the saturated fatty acid content in visceral adipose tissue. In summary, TRF of a HF diet alters the lipidomic profile of plasma, liver, and adipose tissue, creating a third distinct lipid metabolic state indicative of positive metabolic adaptations following HF intake.

Background/aim Time-restricted feeding (TRF) during the dark phase of the day restores metabolic homeostasis in mice. Materials and methods We performed untargeted metabolomic analysis on plasma from mice subjected to TRF that attenuates high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma (LLC). Results Twenty-four of 152 identified metabolites differed among the four dietary groups (non-LLC-bearing mice fed the AIN93G diet and LLC-bearing mice fed the AIN93G, the high-fat diet (HFD), or TRF of the HFD). Component 1 of sparse partial least squares-discriminant analysis showed a clear separation between non-LLC-bearing and LLC-bearing mice. Major metabolites responsible for the changes were elevations in α-tocopherol, docosahexaenoic acid, cholesterol, dihydrocholestrol, isoleucine, leucine, and phenylalanine and decreases in lactic acid and pyruvic acid in LLC-bearing mice particularly those fed the HFD. Time-restricted feeding shifted the metabolic profile of LLC-bearing mice towards that of non-LLC-bearing controls. Conclusion Time-restricted feeding improves metabolic profile of LLC-bearing mice.

Dietary fiber has numerous health benefits, such as increasing satiety, and is regularly included in healthy dietary recommendations. However, different types and sources of fiber vary in their chemical properties and biological effects. This double-blind, randomized, placebo-controlled, crossover study investigated the effects of resistant starch type 2 (RS2) from wheat on self-reported perceptions of satiety and associated gut hormones in 30 healthy adults ages 40-65 years of age. Participants consumed rolls made using either RS2-enriched wheat flour or a wild-type flour for one week before a test day during which they ate a mixed meal containing the same roll type. Both self-reported perceptions of satiety and plasma concentrations of gut hormones were measured following the meal to assess whether the RS2-enriched wheat enhanced satiety and suppressed hunger for a longer period than the control wheat. Exploratory analysis indicated that fasting and peak concentration of peptide YY3-36 (PYY3-36; qfast = 0.02, qpeak = 0.02) increased, while peak concentration and iAUC of glucose-dependent insulinotropic peptide (GIP; qpeak < 0.001, qiAUC < 0.001) decreased after ingesting RS2-enriched wheat. However, self-reported perceptions of hunger or fullness using visual analog scales (VAS) did not differ following the test meal.

Microbial dysbiosis and increased intestinal permeability are targets for prevention or reversal of weight gain in high-fat (HF) diet-induced obesity (DIO). Prebiotic milk oligosaccharides (MO) have been shown to benefit the host intestine but have not been used in DIO. We hypothesized that supplementation with bovine MO would prevent the deleterious effect of HF diet on the gut microbiota and intestinal permeability and attenuate development of the obese phenotype. C57BL/6 mice were fed a control diet, HF (40% fat/kcal), or HF + prebiotic [6%/kg bovine milk oligosaccharides (BMO) or inulin] for 1, 3, or 6 wk. Gut microbiota and intestinal permeability were assessed in the ileum, cecum, and colon. Addition of BMO to the HF diet significantly attenuated weight gain, decreased adiposity, and decreased caloric intake; inulin supplementation also lowered weight gain and adiposity, but this did not reach significance. BMO and inulin completely abolished the HF diet-induced increase in paracellular and transcellular permeability in the small and large intestine. Both BMO and inulin increased abundance of beneficial microbes Bifidobacterium and Lactobacillus in the ileum. However, inulin supplementation altered phylogenetic diversity and decreased species richness. We conclude that addition of BMO to the HF diet completely prevented increases in intestinal permeability and microbial dysbiosis and was partially effective to prevent weight gain in DIO. NEW & NOTEWORTHY This study provides the first report of the effects of prebiotic bovine milk oligosaccharides on the host phenotype of high-fat diet-induced obesity in mice.

Secondary bile acids (BAs) and short chain fatty acids (SCFAs), two major types of bacterial metabolites in the colon, cause opposing effects on colonic inflammation at chronically high physiological levels. Primary BAs play critical roles in cholesterol metabolism, lipid digestion, and host–microbe interaction. Although BAs are reabsorbed via enterohepatic circulation, primary BAs serve as substrates for bacterial biotransformation to secondary BAs in the colon. High-fat diets increase secondary BAs, such as deoxycholic acid (DCA) and lithocholic acid (LCA), which are risk factors for colonic inflammation and cancer. In contrast, increased dietary fiber intake is associated with anti-inflammatory and anticancer effects. These effects may be due to the increased production of the SCFAs acetate, propionate, and butyrate during dietary fiber fermentation in the colon. Elucidation of the molecular events by which secondary BAs and SCFAs regulate colonic cell proliferation and inflammation will lead to a better understanding of the anticancer potential of dietary fiber in the context of high-fat diet-related colon cancer. This article reviews the current knowledge concerning the effects of secondary BAs and SCFAs on the proliferation of colon epithelial cells, inflammation, cancer, and the associated microbiome.

Breast cancer is a rare but aggressive disease in men. Approximately, 90% of all breast cancer in men are invasive carcinomas, 25% of which have distant metastasis at the time of clinical presentation. Obesity is a risk factor for breast cancer. Monocyte chemotactic protein-1 (MCP-1) is an adipose-derived cytokine whose concentrations are elevated by obesity. This study tested the hypothesis that adipose-derived MCP-1 contributes to male breast cancer. In a 2x2 design, male MMTV-PyMT mice with or without adipose specific Mcp-1 knockdown [designated as Mcp-1-/- or wild-type (WT)] were fed the standard AIN93G diet or an obesogenic, high-fat diet (HFD) for 25 weeks. The AIN93G diet and HFD contained 16% and 45% of energy from soybean oil, respectively. Mcp-1-/- mice had lower adipose Mcp-1 expression than WT mice. Adipose Mcp-1 deficiency reduced plasma concentrations of MCP-1 in mice fed the HFD. Mice fed the HFD had a greater tumor progression rate than mice fed the AIN93G diet (4679% vs 2430%), regardless of genotype. Mcp-1-/- mice, compared to WT mice, had a longer tumor latency (25.2 weeks vs 18.0 weeks) and lower tumor incidence (19% vs 56%), tumor progression rate (2317% vs 4792%), and tumor weights (0.23 g vs 0.64 g). Metabolomic analysis of plasma identified 87 metabolites, 56 of which differed among the four groups, including 24 that differed between the diets and 22 that differed between the genotypes. Sparse partial least squares-discriminant analysis identified 10 major metabolites that were altered the most among the four groups. These included amino acids (alanine, isoleucine, leucine, phenylalanine, threonine, and valine) and carbohydrate metabolites (fumaric acid, glucuronic acid, hexuronic acid, and malic acid). The integrated pathway analysis of the 87 identified metabolites showed that protein biosynthesis and carbohydrate metabolism pathways are the most disturbed in MMTV-PyMT mice. In conclusion, adipose-derived MCP-1 contributes to mammary tumorigenesis and alters metabolism in male MMTV-PyMT mice. Citation Format: Lin Yan, Sneha Sundaram, Bret M. Rust, Matthew J. Picklo, Michael R. Bukowski. Tumorigenic and metabolomic impacts of adipose-derived monocyte chemotactic protein-1 in a model of obesity-enhanced, male breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2561.

Erratic eating behavior disrupts diurnal rhythms of metabolism and may contribute to obesity. Time-restricted feeding (TRF), in which food is available in the active period of the day (the dark phase for nocturnal animals), restores metabolic homeostasis in mice. In a mouse model of Lewis lung carcinoma (LLC), we found that TRF (12 hours, dark phase) attenuates obesity-enhanced spontaneous metastasis to the lungs in a study that compared differences in the extent of metastasis among four dietary groups: non-LLC-bearing mice fed the standard AIN93G diet and LLC-bearing mice fed the AIN93G, an obesogenic high-fat diet (HFD) or TRF with the HFD. With the goal of determining potential plasma fingerprints underlying TRF efficacy, we performed untargeted metabolomic analysis upon the plasma samples from this study. Using gas chromatography time-of-flight mass spectrometry, we identified 152 compounds of which 24 differed among the four groups. Ten analytes that were the most influential in treatment separation were alpha-tocopherol, phenylalanine, isoleucine, leucine, pyruvic acid, dihydrocholestrol, arachidonic acid (ARA), docosahexaenoic acid (DHA), lactic acid, and cholesterol. In mice fed the AIN93G diet, compared to non-LLC-bearing mice LLC elevated alpha-tocopherol, ARA, isoleucine, phenylalanine, cholesterol, lauric acid, and 4-hydroxybenzoate and decreased lactic acid, lactamide, and pyruvic acid. In LLC-bearing mice, compared to the AIN93G diet the HFD elevated asparagine, leucine, phenylalanine, dehydrocholesterol, p-cresol sulfate, and hexuronic acid and decreased 1,5-anhydroglucitol, palmitoleic acid, myristic acid, lauric acid, and 4-hydrobenzoate. Compared to the HFD, TRF elevated linoleic acid and 2-hydroxyhexanoic acid and decreased alpha-tocopherol, asparagine, isoleucine, leucine, phenylalanine, dihydrocholesterol, p-cresol sulfate, hexuronic acid, and DHA. This study showed that LLC metastatic growth and an increase in dietary fat consumption disrupted metabolic homeostasis, as reflected in plasma analyte changes compared to their respective controls. TRF, through its temporal regulation of food intake, restored HFD-mediated metabolic disruption and may have contributed to its inhibition of obesity-enhanced LLC metastasis. Citation Format: Lin Yan, Bret M. Rust, Matthew J. Picklo. Plasma metabolomic changes in mice with time restricted feeding-attenuated pulmonary metastasis of Lewis lung carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3457.

Background Since 2005, the Dietary Guidelines for Americans have recommended consuming at least half of total grains as whole grains (WGs) for optimal health benefits; however, consumption of WGs falls far short of recommended amounts. Objective This study aimed to evaluate the effect of mere exposure to WGs on liking, acceptability, and consumption of WG foods and to determine if exposure to WG would influence liking and wanting for other foods varying in fat content and sweet taste. Methods Healthy, self-identified low WG consumers (n = 45) were randomly assigned to either a 6-wk WG intervention or a refined grain (RG) control condition during which they received a weekly market basket of grain products to incorporate into daily meals and snacks. Consumption of grain products was measured by weekly logs and weigh-backs. A sensory evaluation protocol was conducted at baseline and week 6 to evaluate changes in perception of grain products. Computer tasks designed to measure liking and wanting for other foods varying in high/low-fat content and sweet/savory taste were also completed at baseline and week 6. Results Participants in the WG group significantly increased WG consumption. Exposure to WG products resulted in improved ratings of liking, flavor, texture, and willingness to include WG in the regular diet. No significant changes in liking or wanting for foods representing high-fat sweet (HFSW), low-fat sweet (LFSW), high-fat savory (HFSA), or low-fat savory (LFSA) categories were found in the WG group. In contrast, exposure to RG foods resulted in an increased explicit wanting for HFSW and LFSW and a decreased wanting for HFSA foods. Conclusions Mere exposure to WG foods represents a feasible and easily applied behavioral strategy for increasing consumption of WGs. Encouraging consumers to focus on enjoyment of the taste may be more effective than emphasizing the health benefits of WG consumption. This trial was registered at clinicaltrials.gov as NCT01403857.

Increased amylose in wheat (Triticum ssp.) starch is associated with increased resistant starch, a fermentable dietary fiber. Fermentation of resistant starch in the large intestine produces short-chain fatty acids that are associated with human health benefits. Since wheat foods are an important component of the human diet, increases in amylose and resistant starch in wheat grains have the potential to deliver health benefits to a large number of people. In three replicated field trials we found that mutations in starch branching enzyme II genes (SBEIIa and SBEIIb) in both A and B genomes (SBEIIa/b-AB) of durum wheat [T. turgidum L. subsp. durum (Desf.) Husn.] resulted in large increases of amylose and resistant starch content. The presence of these four mutations was also associated with an average 5% reduction in kernel weight (P = 0.0007) and 15% reduction in grain yield (P = 0.06) compared to the wild type. Complete milling and pasta quality analysis showed that the mutant lines have an acceptable quality with positive effects on pasta firmness and negative effects on semolina extraction and pasta color. Positive fermentation responses were detected in rats (Rattus spp.) fed with diets incorporating mutant wheat flour. This study quantifies benefits and limitations associated with the deployment of the SBEIIa/b-AB mutations in durum wheat and provides the information required to develop realistic strategies to deploy durum wheat varieties with increased levels of amylose and resistant starch.

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This study was designed to determine if providing wheat, corn, and rice as whole (WG) or refined grains (RG) under free-living conditions will change parameters of health over a six-week intervention in healthy, habitual non-WG consumers. Measurements of body composition, fecal microbiota, fasting blood glucose, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides were made at baseline and post intervention. Subjects were given adequate servings of either WG or RG products based on their caloric need and asked to keep records of grain consumption, bowel movements, and GI symptoms weekly. After six weeks, subjects repeated baseline testing. Significant decreases in total, LDL, and non-HDL cholesterol were seen after the WG treatments but were not observed in the RG treatment. During Week 6, bowel movement frequency increased with increased WG consumption. No significant differences in microbiota were seen between baseline and post intervention, although, abundance of order Erysipelotrichales increased in RG subjects who ate more than 50% of the RG market basket products. Increasing consumption of WGs can alter parameters of health, but more research is needed to better elucidate the relationship between the amount consumed and the health-related outcome.

OBJECTIVES: Evidence suggests that the amount of fatty acid saturation and chain length affect fatty acid oxidation. Metabolism of unsaturated fatty acids may increase energy expenditure and shorter chain fatty acids may be selectively oxidized more readily. More data are needed to determine the impact of fatty acids, as they exist in dietary fats and oils, upon energy expenditure. We tested differences in energy expenditure after an acute meal challenge prepared with dietary fats and oils with fatty acids of differing chain lengths and saturation. The fats and oils used included olive oil (OO, for oleic acid, 18:1n-9), flaxseed oil (FL, for alpha-linolenic acid, 18:3n-3), sunflower oil (SO, for linoleic acid, 18:2n-6), heavy cream (HC, for saturated fatty acids) and fish oil (FO, for docosahexaenoic acid, 22:6n-3). METHODS: Healthy men and women (N = 27; 56% men; age: 26.8 ± 6.8; BMI: 29.1 ± 3.2), participated in a five-way crossover trial with intention to treat analysis. Body composition was assessed prior to the first study visit by dual X-ray absorptiometry. A standard three-day lead-in diet, prescribed for the participants’ energy needs, was consumed prior to testing. Subjects entered the metabolic chamber the evening before testing and were awakened at 6 AM for a resting metabolic rate measurement followed by a four-hour meal challenge. Test days were separated by at least 7 days. A 500 kcal smoothie with 30 g of test fat source was consumed within 15 min of an initial fasting blood draw. Metabolic rate (MR) and oxidation rates for fat, carbohydrate and protein were analyzed with proprietary software (PiLR™; MEI Research, Ltd.) for four hours after the challenge. RESULTS: MR standardized to fat free mass (FFM) and independent of FFM was greater after HC (1.64 ± 0.24 kcal/min) than FL (1.55 ± 0.26 kcal/min) and OO (1.53 ± 0.24 kcal/min) (P

OBJECTIVES: Obesity and obesity-related disease contribute to health care costs and pose serious health risks. Rodent studies indicate that time-restricted feeding (TRF) may be effective in reducing adiposity and metabolic disease associated with obesity. However, the metabolic pathways impacted by TRF in the context of obesogenic, high-fat (HF) diets need clarity. In the present work we examined the metabolomic changes in plasma induced by TRF of a HF diet in mice compared to a HF diet eaten ad libitum (AL) vs AL intake of a low-fat (LF) control diet. METHODS: Male mice (12 weeks old) were fed a LF-AL diet (16%en fat), a HF-AL diet (48%en fat) or a HF diet restricted to feeding for 12 hours per day during the dark phase (HF-TRF). In week 9 of the study, energy expenditure data were collected. After 12 weeks, animals were fasted and plasma collected for clinical chemistries and metabolomic analysis. Multivariate analysis was used to discriminate diet treatments in untargeted metabolomic data. RESULTS: Energy expenditure measurements throughout the day showed a markedly reduced fasting respiratory exchange ratio (RER) in HF-TRF mice during the inactive (light) phase compared to AL groups. Measures of insulin resistance, while increased with HF-AL intake, were resolved in the HF-TRF group. Partial least squares discriminant analysis revealed plasma non-esterified fatty acids (NEFA) and amino acids (AA) to be important discriminators between diet treatments. TRF resulted in elevated NEFA concentrations of the saturated fatty acids (12:0 to 18:0) and the polyunsaturated fatty acids α-linolenic acid and linoleic acid compared to HF-AL. Conversely, the concentrations of aromatic and branched chain amino acids were reduced in HF-TRF mice compared to HF-AL mice. CONCLUSIONS: Alterations in plasma metabolites following TRF of a HF diet are consistent with greater lipid utilization during the inactive phase as reflected in the RER. Decreases in the aromatic and branched chain amino acid concentrations are consistent with improved insulin sensitivity in humans. FUNDING SOURCES: This work was supported by USDA-ARS project 3062-51000-053-00D. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

Increased amylose in wheat (Triticum ssp.) starch is associated with increased resistant starch, a fermentable dietary fiber. Fermentation of resistant starch in the large intestine produces short-chain fatty acids that are associated with human health benefits. Since wheat foods are an important component of the human diet, increases in amylose and resistant starch in wheat grains have the potential to deliver health benefits to a large number of people. In three replicated field trials we found that mutations in starch branching enzyme II genes (SBEIIa and SBEIIb) in both A and B genomes (SBEIIa/b-AB) of durum wheat [T. turgidum L. subsp. durum (Desf.) Husn.] resulted in large increases of amylose and resistant starch content. The presence of these four mutations was also associated with an average 5% reduction in kernel weight (P = 0.0007) and 15% reduction in grain yield (P = 0.06) compared to the wild type. Complete milling and pasta quality analysis showed that the mutant lines have an acceptable quality with positive effects on pasta firmness and negative effects on semolina extraction and pasta color. Positive fermentation responses were detected in rats (Rattus spp.) fed with diets incorporating mutant wheat flour. This study quantifies benefits and limitations associated with the deployment of the SBEIIa/b-AB mutations in durum wheat and provides the information required to develop realistic strategies to deploy durum wheat varieties with increased levels of amylose and resistant starch.

BackgroundGut microbial diversity and abundance can profoundly impact human health.Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obes...