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Background: Previous animal model studies have highlighted a role for cholesterol and its oxidized derivatives (oxysterols) in uterine contractile activity, however, a lipotoxic state associated with hypercholesterolemia may contribute to labor dystocia. Therefore, we investigated if maternal mid-pregnancy cholesterol and oxysterol concentrations were associated with labor duration in a human pregnancy cohort. Methods: We conducted a secondary analysis of serum samples and birth outcome data from healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22–28 weeks of gestation. Serum was analyzed for total-C, HDL-C, and LDL-C by direct automated enzymatic assay and oxysterol profile including 7α-hydroxycholesterol (7αOHC), 7β-hydroxycholesterol (7βOHC), 24-hydroxycholesterol (24OHC), 25-hydroxycholesterol (25OHC), 27-hydroxycholesterol (27OHC), and 7-ketocholesterol (7KC) by liquid chromatography-selected ion monitoring-stable isotope dilution-atmospheric pressure chemical ionization-mass spectroscopy. Associations between maternal second trimester lipids and labor duration (minutes) were assessed using multivariable linear regression adjusting for maternal nulliparity and age. Results: An increase in labor duration was observed for every 1-unit increment in serum 24OHC (0.96 min [0.36,1.56], p < 0.01), 25OHC (7.02 min [1.92,12.24], p = 0.01), 27OHC (0.54 min [0.06, 1.08], p < 0.05), 7KC (8.04 min [2.7,13.5], p < 0.01), and total oxysterols (0.42 min [0.18,0.06], p < 0.01]. No significant associations between labor duration and serum total-C, LDL-C, or HDL-C were observed. Conclusions: In this cohort, mid-pregnancy concentrations of maternal oxysterols (24OHC, 25OHC, 27OHC, and 7KC) were positively associated with labor duration. Given the small population and use of self-reported labor duration, subsequent studies are required for confirmation. [ABSTRACT FROM AUTHOR]

Background: An excessive rise in maternal lipids during pregnancy may have detrimental impacts on maternal and fetal health leading to adverse pregnancy outcomes. However, knowledge gaps exist with respect to the association between lipid biomarkers and birth outcomes. Methods: We conducted a secondary data analysis of healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22–28 weeks of gestation and birth outcome data. Serum was analyzed for conventional lipid profile (total-C, HDL-C, LDL-C, and triglycerides) and lipoprotein subclass distribution, including particle number (nM) and size (nm), for very low-density lipoprotein (VLDL)/chylomicron (CM), low density lipoprotein (LDL), and high-density lipoprotein (HDL), by nuclear magnetic resonance spectroscopy. Associations between maternal lipids and birth outcomes, including birth weight (g) and gestational age (weeks), were assessed using multivariable linear regression, adjusted for pre-pregnancy BMI. Results: Although conventional lipids were not associated (p > 0.05) with birth outcomes, every 1-unit increment in large VLDL/CM particles (nM) and VLDL/CM size (nm) was associated with an increase in birth weight (confounder-adjusted β-coefficient, 45.80 g [5.30, 86.20, p = 0.003] and 24.90 g [8.80, 40.90, p = 0.002], respectively). Among the HDL subclass parameters, a 1-unit (nM) increase in the concentration of total HDL-particles was associated with a reduced birth weight (confounder adjusted β-coefficient, -19.40 g [95% confidence interval, -36.70, -2.20]; p = 0.03) after adjustment for maternal pre-pregnancy BMI. Conclusion: The preliminary results of this pilot study suggest that total particle concentrations of VLDL/CM and HDL in mid-pregnancy have divergent associations with birth weight, potentially reflecting the specific roles of these lipoprotein particles with respect to placental function and fetal growth. [ABSTRACT FROM AUTHOR]

Resistant starch (RS) has been well characterized for its glycemic control properties; however, there is little consensus regarding the influence of RS on blood lipid concentrations and lipoprotein distribution and size. Therefore, this study aimed to characterize the effect of daily RS supplementation in a controlled capsule delivery on biomarkers of cardiovascular (blood lipids, lipoproteins) and diabetes (glucose, insulin) risk in a pig model. Twelve 8-week-old male Yorkshire pigs were placed on a synthetic Western diet and randomly divided into two groups (n = 6/group) for 30 days: (1) a placebo group supplemented with capsules containing unmodified pre-gelatinized potato starch (0 g/RS/day); and (2) an RS group supplemented with capsules containing resistant potato starch (10 g/RS/day). Serum lipids including total-cholesterol (C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides did not differ (p > 0.05) between the RS and placebo groups. Although the total numbers of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles were similar (p > 0.05) between the two groups, total high-density lipoprotein (HDL) particles were higher (+28%, p < 0.05) in the RS group compared with placebo, resulting from an increase (p < 0.05) in the small HDL subclass particles (+32%). Compared with the placebo group, RS supplementation lowered (p < 0.05) fasting serum glucose (−20%) and improved (p < 0.05) insulin resistance as estimated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) without a change in insulin. Additionally, total serum glucagon-like-peptide 1 (GLP-1) was higher (+141%, p < 0.05) following RS supplementation compared with placebo. This data suggests that in addition to the more well-characterized effect of RS intake in lowering blood glucose and improving insulin sensitivity, the consumption of RS may be beneficial in lipid management strategies by enhancing total HDL particle number. [ABSTRACT FROM AUTHOR]

To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (−55%) than either the PS (−24%) or the αLA (−25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (−47%) or in combination with PS (−54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21–22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (+52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone. [ABSTRACT FROM AUTHOR]

Background: In utero exposure to excessive cholesterol has been shown to increase fetal plasma cholesterol concentration and predispose adult offspring to cardiovascular disease (CVD) risk. Because lipid-lowering drugs are contraindicated during pregnancy, natural cholesterol-lowering compounds may be a safe and effective alternative to reduce CVD risk in offspring born to hypercholesterolemic mothers. Objective: This study used the hypercholesterolemic apolipoprotein E-deficient (apoE-/-) mouse model to test the hypothesis that mothers supplemented with phytosterols during gestation and lactation would produce offspring with a more favorable lipid profile than offspring from unsupplemented mothers, despite having a genetic predisposition toward hypercholesterolemia. Methods: Sixteen female apoE-/- mice were randomly assigned to 2 diets fed throughout the gestation and lactation periods: a cholesterol-enriched diet (CH) (0.15%) or the cholesterol-enriched diet supplemented with phytosterols (CH/PS) (2%). Serum lipids and lipoproteins were measured by enzyme assay and nuclear magnetic resonance spectroscopy, respectively, and liver cholesterol was analyzed by GC. Results: Compared with the CH-fed dams at the end of lactation, phytosterol-supplemented dams displayed lower (P< 0.05) serum total cholesterol (-55%), non-HDL cholesterol (-56%), and LDL cholesterol (-47%), but no change (P> 0.05) in HDL cholesterol and triacylglycerol (TG) concentrations. Pups from phytosterol-fed dams demonstrated lower (P< 0.05) total cholesterol (-25%), non-HDL cholesterol (-25%), LDL cholesterol (-47%), and TGs (-41 %), without any change (P> 0.05) in HDL cholesterol compared with pups from CH-fed dams. Furthermore, compared with pups from CH-fed dams, pups from phytosterol-supplemented dams displayed a lower (P< 0.05) number of total LDL particles (-34%), VLDL particles (-31 %), and HDL particles (-30%). Conclusion: Our results in apoE-/- mice suggest that even under strong genetic predisposition to hypercholesterolemia, pups born to mothers supplemented with phytosterols during gestation and lactation exhibit favorable liver and serum lipid responses compared with pups from unsupplemented mothers. [ABSTRACT FROM AUTHOR]

The cholesterol lowering effects of plant sterols and stanols are a well-established complementary means by which to reduce blood cholesterol concentrations. The average reduction in LDL cholesterol concentrations is approximately -10% following a 28-day supplementation protocol. There is very little known regarding what, if any, effect plant sterols and stanols have on other cardiometabolic risk factors such as blood pressure and endothelial function. Here we review the available literature on this topic and attempt to draw conclusions regarding any benefit or risk for blood pressure and endothelial function linked to plant sterol and stanol supplementation. Generally there has been very little work focusing on changes in blood pressure or endothelial function following plant sterol or stanol intervention, but these factors have been measured in some cases as secondary outcomes. Overall, there is little evidence to support either positive or negative effects of plant sterol or stanol supplementation of blood pressure and the data surrounding endothelial function is quite inconclusive. This area of research would benefit from well controlled mechanistic studies in animals and primary interventions in humans which focus on ambulatory blood pressure, central blood pressure and endothelial function. [ABSTRACT FROM AUTHOR]

Phytosterols (PS) have long been recognized for their cholesterol-lowering action, however, recent work has highlighted triglyceride (TG)-lowering responses to PS that may have been overlooked in previous human interventions and mechanistic animal model studies. This review assesses the current state of knowledge regarding the effect of dietary PS supplementation on blood TG concentrations by examining the average therapeutic response, potential mechanisms, and metabolic and genetic factors that may contribute to inter-individual variability. Data from human intervention trials demonstrates that, compared to baseline concentrations, PS supplementation results in a variable TG-lowering response ranging from 0.8 to 28%. It is evident that hypertriglyceridemic individuals (>1.7 mmol/L) have a greater TG-lowering response to PS (11-28%) than subjects with normal plasma TG concentrations (0.8-7%). Although a genetic basis for the variable TG-lowering effects of PS is probable, there are only limited studies to draw on. The available data suggest that polymorphisms in the apolipoprotein E (apoE) gene may affect responsiveness, with PS-induced reductions in TG more readily evident in apoE2 than apoE3 or E4 subjects. Although only a minimal number of animal model studies have been conducted to specifically examine the mechanisms whereby PS may reduce blood TG concentrations, it appears that there may be multiple mechanisms involved including interruption of intestinal fatty acid absorption and modulation of hepatic lipogenesis and very low density lipoprotein packaging and secretion. In summary, the available data suggest that PS may be an effective therapy to lower blood TG, particularly in hypertriglyceridemic individuals. However, before PS can be widely recommended as a TG-lowering therapy, studies that are specifically powered and designed to fully access therapeutic responses and the mechanisms involved are required. [ABSTRACT FROM AUTHOR]

Background In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), however, the underlying mechanisms are not known. Methods We examined the TG-lowering mechanisms of dietary PS in Syrian golden hamsters randomly assigned to a high fat (HF) diet or the HF diet supplemented with PS (2%) for 6 weeks (n = 12/group). An additional subset of animals (n = 12) was provided the HF diet supplemented with ezetimibe (EZ, 0.002%) as a positive control as it is a cholesterollowering agent with known TG-lowering properties. Results In confirmation of diet formulation and compound delivery, both the PS and EZ treatments lowered (p < 0.05) intestinal cholesterol absorption (24 and 31%, respectively), blood non- HDL cholesterol (61 and 66%, respectively), and hepatic cholesterol (45 and 55%, respectively) compared with the HF-fed animals. Blood TG concentrations were lower (p < 0.05) in the PS (49%) and EZ (68%)-treated animals compared with the HF group. The TGlowering response in the PS-supplemented group was associated with reduced (p < 0.05) intestinal SREBP1c mRNA (0.45 fold of HF), hepatic PPARα mRNA (0.73 fold of HF), hepatic FAS protein abundance (0.68 fold of HD), and de novo lipogenesis (44%) compared with the HF group. Similarly, lipogenesis was lower in the EZ-treated animals, albeit through a reduction in the hepatic protein abundance of ACC (0.47 fold of HF). Conclusions Study results suggest that dietary PS are protective against diet-induced hypertriglyceridemia, likely through multiple mechanisms that involve modulation of intestinal fatty acid metabolism and a reduction in hepatic lipogenesis. [ABSTRACT FROM AUTHOR]

Background: Given the highly debated role of dairy food consumption in modulating biomarkers of metabolic syndrome, this study was conducted to examine the influence of long-term (6 month) dairy consumption on metabolic parameters in healthy volunteers under free-living conditions without energy restriction. Methods: Twenty-three healthy subjects completed a randomized, crossover trial of 12 months. Participants consumed their habitual diets and were randomly assigned to one of two treatment groups: a high dairy supplemented group instructed to consume 4 servings of dairy per day (HD); or a low dairy supplemented group limited to no more than 2 servings of dairy per day (LD). Baseline, midpoint, and endpoint metabolic responses were examined. Results: Endpoint measurements of body weight and composition, energy expenditure, blood pressure, blood glucose, and blood lipid and lipoprotein responses did not differ (p > 0.05) between the LD and HD groups. HD consumption improved (p < 0.05) plasma insulin (-9%) and insulin resistance (-11%, p = 0.03) as estimated by HOMA-IR compared with the LD group. Conclusions: Study results suggest that high dairy consumption (4 servings/d) may improve insulin resistance without negatively impacting bodyweight or lipid status under free-living conditions. [ABSTRACT FROM AUTHOR]

Aim: Egg is a major food allergen in childhood. Recent studies suggest that early introduction of allergenic foods can decrease the risk of developing egg allergy. The impact of early egg introduction in the general population is unclear. We examined associations between age of infant egg introduction and childhood egg allergy outcomes in a general population. Methods: The study population consisted of 1217 neonates from Project Viva, a longitudinal pre‐birth cohort in eastern Massachusetts area, USA. Mothers reported age of infant egg introduction and child egg allergy using questionnaires and specific IgE to egg white was assayed. We estimated associations between age of infant egg introduction and egg allergy outcomes using Log‐binomial regression models, adjusting for socio‐demographics and health confounders. Results: Egg allergy at 2 years was significantly higher (8.0% vs. 1.4%, P < 0.0001) in children who had delayed egg introduction beyond infancy, compared with children who were introduced to egg during infancy (adjusted relative risk or aRR 7.58; 95% CI 3.08, 18.61). At 12 years, the risk of egg allergy remained significantly higher (3.9% vs. 1.1%, P = 0.048) in children with delayed egg introduction compared with children introduced to egg during infancy (aRR 4.07; 95% CI 1.20, 13.87). Conclusions: Infants with delayed introduction of eggs after 12 months had increased risk of egg allergy in childhood (2 years) and the relationship persisted in early adolescence (12 years). Our findings suggest that introduction to eggs before 12 months could contribute to the prevention of egg allergy. [ABSTRACT FROM AUTHOR]

Alpha lipoic acid (α-LA) is a potent biological antioxidant that is found naturally in the human body at very low concentrations, primarily in the mitochondria. However, synthetic α-LA is commercially available as a nutritional supplement and has been shown to be effective at ameliorating symptoms in diseases with an underlying oxidative stress component. High blood cholesterol is a major cardiovascular disease (CVD) risk factor and is responsive to diet and lifestyle modifications. In addition to high blood cholesterol, there is increasing evidence that supports the independent role of oxidized lipids and lipoproteins, chiefly oxidized low-density lipoproteins (Ox-LDL), in the development of CVD. Lowering total blood cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG) and raising high-density lipoprotein cholesterol (HDL-C) levels is the most desirable metabolic state for maximum protection against CVD, but can be difficult to achieve through diet and exercise alone. With emerging evidence of reduced LDL-C and TG, increased HDL-C, and blunting of oxidative susceptibility of lipoproteins by α-LA, its use alone or in combination with other dietary supplements may be an effective strategy to modulate multiple metabolic targets of oxidative stress and cholesterol metabolism to reduce CVD risk. This review examines the current evidence for the use of α-LA in CVD risk reduction and identifies the remaining gaps that must be addressed in this area of research. [ABSTRACT FROM AUTHOR]

Reducing intestinal cholesterol absorption with plant sterol consumption is a well-characterized strategy to lower LDL-C and potentially reduce cardiovascular disease risk. However, over 50 years of clinical research demonstrate that there is significant heterogeneity in the individual LDL-C lowering response to plant sterol therapy. A clear understanding of why plant sterols work effectively in some individuals but not in others will ensure optimal integration of plant sterols in future personalized nutritional lipid-lowering strategies. This review will examine the current knowledge base surrounding the metabolic and genetic determinants of LDL-C lowering in response to plant sterol consumption. [ABSTRACT FROM AUTHOR]

Abstract: Many low-income consumers face a limited budget for food purchases. The United States Department of Agriculture developed the Thrifty Food Plan to address this problem of consuming a healthy diet given a budget constraint. This dietary optimization program uses common food choices to build a suitable diet. In this article, the United States Department of Agriculture data sets are used to test the feasibility of consuming a Paleolithic diet given a limited budget. The Paleolithic diet is described as the diet that humans are genetically adapted to, containing only the preagricultural food groups of meat, seafood, fruits, vegetables, and nuts. Constraints were applied to the diet optimization model to restrict grains, dairy, and certain other food categories. Constraints were also applied for macronutrients, micronutrients, and long-chain polyunsaturated fatty acids. The results show that it is possible to consume a Paleolithic diet given the constraints. However, the diet does fall short of meeting the daily recommended intakes for certain micronutrients. A 9.3% increase in income is needed to consume a Paleolithic diet that meets all daily recommended intakes except for calcium. [Copyright &y& Elsevier]

The effect of dietary plant sterols on cholesterol homeostasis has been well characterized in the intestine, but how plant sterols affect lipid metabolism in other lipid-rich tissues is not known. Changes in hepatic cholesterol homeostasis in response to high dietary intakes of plant sterols were determined in male golden Syrian hamsters fed hypercholesterolemia-inducing diets with and without 2% plant sterols (wt:wt; Reducol, Forbes Meditech) for 28 d. Plasma and hepatic cholesterol concentrations, cholesterol biosynthesis and absorption, and changes in the expression of sterol response element binding protein 2 (SREBP2) and liver X receptor-beta (LXRbeta) and their target genes were measured. Plant sterol feeding reduced plasma total cholesterol, non-HDL cholesterol, and HDL cholesterol concentrations 43% (P < 0.0001), 60% (P < 0.0001), and 21% (P = 0.001), respectively, compared with controls. Furthermore, there was a 93% reduction (P < 0.0001) in hepatic total cholesterol and >6-fold (P = 0.029) and >2-fold (P < 0.0001) increases in hepatic beta-sitosterol and campesterol concentrations, respectively, in plant sterol-fed hamsters compared with controls. Plant sterol feeding also increased fractional cholesterol synthesis >2-fold (P < 0.03) and decreased cholesterol absorption 83% (P < 0.0001) compared with controls. Plant sterol feeding increased hepatic protein expression of cytosolic (inactive) SREBP2, decreased nuclear (active) SREBP2, and tended to increase LXRbeta (P = 0.06) and ATP binding cassette transporter G5, indicating a differential modulation of the expression of proteins central to cholesterol metabolism. In conclusion, high-dose plant sterol feeding of hamsters changes hepatic protein abundance in favor of cholesterol excretion despite lower hepatic cholesterol concentrations and higher cholesterol fractional synthesis. [ABSTRACT FROM AUTHOR]

To gain insight into the regulation of hepatic sterol-responsive genes that are thought to mediate the hypocholesterolemic effects of guar gum (GG) consumption, the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), LDL receptor (LDLr), and scavenger receptor class B, type 1 (SR-B1) were examined in pigs consuming an atherogenic control diet or the control diet supplemented with 10% GG. Compared with the control group, GG consumption reduced (P < 0.05) plasma total cholesterol and LDL cholesterol concentrations by 27 and 37%, respectively. Furthermore, hepatic free cholesterol concentration was lower (P < 0.05) in the GG-fed pigs in comparison with the control group. GG consumption increased hepatic LDLr mRNA (1.5-fold of the control, P = 0.09) and protein (2-fold of the control, P < 0.05) expression in comparison with the control group. However, GG consumption reduced hepatic SR-B1 mRNA to 36% of the control (P < 0.05) expression but did not affect (P = 0.19) SR-B1 protein abundance in comparison with the control group. Although SREBP2 mRNA expression was similar (P = 0.89) in the 2 groups, GG consumption increased (P < 0.05) the expression of the cytoplasmic precursor (3-fold of the control) and nuclear active forms (1.5-fold of the control) of SREBP2. We conclude that the hypocholesterolemic effects of GG consumption are related to a reduction in hepatic free cholesterol concentration and associated increases in nuclear active SREBP2 expression and hepatic LDLr abundance. [ABSTRACT FROM AUTHOR]

The author comments on the article "Long-chain acyl-CoA synthetase 6 regulates lipid synthesis and mitochondrial oxidative capacity in human and rat skeletal muscle," by B. G. Teodoro and colleagues. Topics discussed include the conversion of long chain fatty acids (LCFAs) into acyl-CoA synthetase (ACSL), synthesis of skeletal muscle lipids, and the role of intramyocellular lipid concentration in the induction of insulin resistance.

Background: Given the highly debated role of dairy food consumption in modulating biomarkers of metabolic syndrome, this study was conducted to examine the influence of long-term (6 month) dairy consumption on metabolic parameters in healthy volunteers under free-living conditions without energy restriction.Methods: Twenty-three healthy subjects completed a randomized, crossover trial of 12 months. Participants consumed their habitual diets and were randomly assigned to one of two treatment groups: a high dairy supplemented group instructed to consume 4 servings of dairy per day (HD); or a low dairy supplemented group limited to no more than 2 servings of dairy per day (LD). Baseline, midpoint, and endpoint metabolic responses were examined.Results: Endpoint measurements of body weight and composition, energy expenditure, blood pressure, blood glucose, and blood lipid and lipoprotein responses did not differ (p > 0.05) between the LD and HD groups. HD consumption improved (p < 0.05) plasma insulin (-9%) and insulin resistance (-11%, p = 0.03) as estimated by HOMA-IR compared with the LD group.Conclusions: Study results suggest that high dairy consumption (4 servings/d) may improve insulin resistance without negatively impacting bodyweight or lipid status under free-living conditions.Trial Registration: Clinical Trials.gov: NCT01761955. [ABSTRACT FROM AUTHOR]

It is increasingly clear that North Americans prefer dietary approaches to enhance health in favour of pharmaceutical approaches. Although the incorporation of phytosterols (PS) into various food matrices has been effective in lowering cholesterol, the lipid-lowering potential of PS-enriched soymilk has not been investigated. Therefore, the objective of this study was to examine the lipid-lowering efficacy of a PS-enriched soymilk beverage in comparison to a 1% dairy milk control. Twenty-three hypercholesterolemic subjects consumed 3 tetrapacks per day of a PS-enriched soy beverage (1.95g PS/d) or a 1% dairy milk control. The study was conducted as a 28 d controlled dietary intervention according to a two-period cross-over design. Total cholesterol was reduced by 12% (P< 0.0001) in the PS-enriched soymilk group (5.59±0.27 mmol/L) in comparison to the milk control (6.28±0.27 mmol/L). PS-enriched soymilk consumption did not affect HDL cholesterol concentrations but did reduce (P<0.0001) LDL cholesterol by 16% compared to the control group (3.60 vs. 4.20 mmol/L). Plasma triglyceride concentration was reduced (P =0.02) by 9.4% in response to the PS-enriched soy beverage in comparison to the milk control. We conclude that consumption of a PS-enriched soy beverage is an effective dietary strategy to reduce circulating lipid levels in hypercholesterolemic individuals. Supported by WhiteWave Foods Company. [ABSTRACT FROM AUTHOR]

The relationship between the thermal-physical properties of resistant starch and the efficiency of nutrient utilization and intestinal fermentation was examined in pigs fed resistant corn starch, granular resistant potato starch or retrograded resistant corn starch for 30 d according to a completely randomized block design. Nutrient utilization and cecal short-chain fatty acid concentrations were measured with mass balance and gas chromatography-mass spectrometry, respectively. Thermal physical analyses of the selected starches, including onset and peak temperatures and enthalpy changes, were measured with differential scanning calorimetry. Apparent crude protein digestibility values associated with the RS varieties were negatively correlated (P=0.05; r=-0.45) with enthalpy change while Ca and P digestibility values were positively correlated (P<0.05; r=0.44-0.66) with onset and peak temperatures. Cecal butyrate concentrations were positively correlated (P<0.05; r = 0.63-0.83) with onset and peak temperatures and enthalpy changes in the RS varieties. Thermal physical properties associated with the RS varieties, including onset and peak temperatures and enthalpy change, may be useful markers for developing future RS products with specific physiological functions and nutritional roles. [ABSTRACT FROM AUTHOR]

The mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2) and low density lipoprotein receptor (LDLr) were examined in pigs fed an atherogenic control diet or the control diet supplemented with 10% guar gum (GG). Compared to the control group, GG consumption reduced (P<0.05) plasma total cholesterol (27%), LDL cholesterol (37%), and hepatic free cholesterol concentrations. GG consumption increased hepatic LDLr mRNA (1.8 fold, P=0.09) and protein (2 fold, P<0.05) expression in comparison to the control group. Hepatic SREBP2 mRNA expression was not altered (P>0.05) in response to GG consumption. While expression of the cytoplasmic mature form of SREBP2 was similar (P>0.05) between the two groups, GG consumption increased (P<0.05) the expression of the cytoplasmic precursor (3 fold) and nuclear active forms (1.5 fold) of the SREBP2. We conclude that a reduction in hepatic free cholesterol concentration in response to GG consumption enhances nuclear SREBP2 expression by post-transcriptional events that are independent of the proteolytic release of the mature protein from the golgi apparatus. Furthermore, accumulation of nuclear SREBP2 increases the expression of hepatic LDLr and mediates the hypocholesterolemic effects associated with GG consumption. [ABSTRACT FROM AUTHOR]

To evaluate the relationship between infant age of egg introduction and malnutrition‐related growth outcomes in the United States, we analysed secondary data of 1716 mother–child dyads in the Infant Feeding Practices Study II and its Year 6 Follow‐Up Study. Malnutrition‐related growth outcomes included body mass index z‐score (BMIZ), obesity (weight‐for‐height z‐score [WHZ] ≥3 or BMIZ ≥ 2), WHZ, wasting (WHZ < −2), height‐for‐age z‐score (HAZ), and stunting (HAZ < –2). Infant age at egg introduction was analysed as a continuous variable. We used generalised estimating equations to estimate the mean difference in continuous outcomes and relative risk [RR]) for binary outcomes, adjusting for related maternal and child confounders. We also explored interactions with child sex, maternal race/ethnicity, maternal educational level, ever breastfeeding, and formula feeding. In the total sample, a later infant age at egg introduction was associated with a lower mean difference in HAZ (confounder‐adjusted mean difference = −0.08, 95% confidence interval [CI]: −0.12 to −0.03 per month) and a higher risk of stunting (confounder‐adjusted RR = 1.17, 95% CI: 1.03–1.33 per month) at 6 years. The associations between infant age at egg introduction and 12‐month growth outcomes differed by child sex. Among females but not among males, later introduction of eggs was associated with a lower mean WHZ (−0.06 [−0.12 to 0.00] per month) at 12 months. Later egg introduction during infancy was associated with a lower mean HAZ and a higher risk of stunting in 6‐year‐old children. Besides this, it was associated with a lower WHZ among females at 12 months. Key messages: This secondary data analysis evaluated the relationship between infant age at egg introduction and malnutrition‐related growth outcomes among young US children within the Infant Feeding Practices Study II and its Year 6 Follow‐up Study.In the total sample, a later infant age at egg introduction was associated with a lower mean 6‐year height‐for‐age z‐score and a higher risk of stunting at 6 years.The associations between infant age at egg introduction and 12‐month growth outcomes differed by child sex. Later introduction of eggs was associated with a lower mean weight‐for‐height z‐score among females. However, this association was not observed among males. [ABSTRACT FROM AUTHOR]

During the absorptive state, the liver stores excess glucose as glycogen and synthesizes fatty acids for triglyceride synthesis for export as very low density lipoproteins. For de novo synthesis of fatty acids from glucose, the mitochondrial pyruvate dehydrogenase complex (PDC) is the gatekeeper for the generation of acetyl-CoA from glucose-derived pyruvate. Here, we tested the hypothesis that limiting the supply of PDC-generated acetyl-CoA from glucose would have an impact on expression of key genes in the lipogenic pathway. In the present study, although the postnatal growth of liver-specific PDCdeficient (L-PDCKO) male mice was largely unaltered, the mice developed hyperinsulinemia with lower blood glucose levels in the fed state. Serum and liver lipid triglyceride and cholesterol levels remained unaltered in L-PDCKO mice. Expression of several key genes (ACL, ACC1) in the lipogenic pathway and their upstream regulators (LXR, SREBP1, ChREBP) as well as several genes in glucose metabolism (Pklr, G6pd2, Pck1) and fatty acid oxidation (FAT, Cpt1a) was downregulated in livers from L-PDCKO mice. Interestingly, there was concomitant upregulation of lipogenic genes in adipose tissue from L-PDCKO mice. Although, the total hepatic acetyl-CoA content remained unaltered in L-PDCKO mice, modified acetylation profiles of proteins in the nuclear compartment suggested an important role for PDC-generated acetyl-CoA in gene expression in de novo fatty acid synthesis in the liver. This finding has important implications for the regulation of hepatic lipid synthesis in pathological states. [ABSTRACT FROM AUTHOR]

Recent work suggests that plant sterol (PS) consumption may lower triglyceride (TG) concentrations; however, human clinical trial evidence is inconsistent. We associated SNP r5882 in cholesteryl ester transfer protein with changes in TG concentrations following PS consumption (2 g/day for 4 weeks) in a dual-centre, single-blind, randomized, crossover trial. TG concentrations were lowered in homozygotes for the minor G-allele of rs5882 (-0.46 ± 0.13 mmol/L, p = 0.002, n = 10); there was no effect in the A-allele carriers. [ABSTRACT FROM AUTHOR]

Maternal hypercholesterolemia (MHC), a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during pregnancy, may influence offspring hepatic lipid metabolism and increase the risk of nonalcoholic fatty liver disease (NAFLD). As NAFLD is characterized by a sexual dimorphic response, we assessed whether early-life exposure to excessive cholesterol influences the development of NAFLD in offspring and whether this occurs in a sex-specific manner. Female apoE-/- mice were randomly assigned to a control (CON) or a high cholesterol (CH; 0.15%) diet prior to breeding. At parturition, a cross-fostering approach was used to establish three groups: (1) normal cholesterol exposure throughout gestation and lactation (CON-CON); (2) excessive cholesterol exposure throughout gestation and lactation (CH-CH); and (3) excessive cholesterol exposure in the gestation period only (CH-CON). Adult male offspring (PND 84) exposed to excessive cholesterol during gestation only (CH-CON) demonstrated hepatic triglyceride (TG) accumulation and reduced lipogenic gene expression. However, male mice with a prolonged cholesterol exposure throughout gestation and lactation (CH-CH) had a similar, but not exacerbated hepatic response. Further, with the exception of higher serum TG in adult CH-CH females, evidence for a programming effect in female offspring was largely absent in comparison with males. These results indicate a sexual dimorphic response with respect to the effect of MHC on later life hepatic steatosis and highlight the gestation period as the most influential malprogramming window for hepatic lipid dysfunction in males. [ABSTRACT FROM AUTHOR]

The Pyruvate Dehydrogenase Complex (PDC), a key enzyme in glucose metabolism, catalyzes an irreversible oxidative decarboxylation reaction of pyruvate to acetyl- CoA, linking the cytosolic glycolytic pathway to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Earlier we reported a down-regulation of several key hepatic lipogenic enzymes and their upstream regulators in liver-specific PDC-deficient mouse (L-PDCKO model by deleting the Pdha1 gene). In this study we investigated gene expression profiles of key glycolytic enzymes and other proteins that respond to various metabolic stresses in liver from L-PDCKO mice. Transcripts of several, such as hexokinase 2, phosphoglycerate kinase 1, pyruvate kinase muscletype 2, and lactate dehydrogenase B as well as those for the nonglycolysis-related proteins, CD-36, C/EBP homologous protein, and peroxisome proliferator-activated receptor γ, were up-regulated in L-PDCKO liver whereas hypoxia-induced factor-1α, pyruvate dehydrogenase kinase 1 and Sirtuin 1 transcripts were down-regulated. The protein levels of pyruvate kinase muscle-type 2 and lactate dehydrogenase B were increased whereas that of lactate dehydrogenase A was decreased in PDC-deficient mouse liver. Analysis of endoplasmic reticulum and oxidative stress indicators suggests that the L-PDCKO liver showed evidence of the former but not the latter. These findings indicate that (i) liver-specific PDC deficiency is sufficient to induce "aerobic glycolysis characteristic" in mouse liver, and (ii) the mechanism(s) responsible for these changes appears distinct from that which induces the Warburg effect in some cancer cells. [ABSTRACT FROM AUTHOR]

The Pyruvate Dehydrogenase Complex (PDC), a key enzyme in glucose metabolism, catalyzes an irreversible oxidative decarboxylation reaction of pyruvate to acetyl‐CoA, linking the cytosolic glycolytic pathway to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Earlier we reported a down‐regulation of several key hepatic lipogenic enzymes and their upstream regulators in liver‐specific PDC‐deficient mouse (L‐PDCKO model by deleting the Pdha1 gene). In this study we investigated gene expression profiles of key glycolytic enzymes and other proteins that respond to various metabolic stresses in liver from L‐PDCKO mice. Transcripts of several, such as hexokinase 2, phosphoglycerate kinase 1, pyruvate kinase muscle‐type 2, and lactate dehydrogenase B as well as those for the nonglycolysis‐related proteins, CD‐36, C/EBP homologous protein, and peroxisome proliferator‐activated receptor γ, were up‐regulated in L‐PDCKO liver whereas hypoxia‐induced factor‐1α, pyruvate dehydrogenase kinase 1 and Sirtuin 1 transcripts were down‐regulated. The protein levels of pyruvate kinase muscle‐type 2 and lactate dehydrogenase B were increased whereas that of lactate dehydrogenase A was decreased in PDC‐deficient mouse liver. Analysis of endoplasmic reticulum and oxidative stress indicators suggests that the L‐PDCKO liver showed evidence of the former but not the latter. These findings indicate that (i) liver‐specific PDC deficiency is sufficient to induce “aerobic glycolysis characteristic” in mouse liver, and (ii) the mechanism(s) responsible for these changes appears distinct from that which induces the Warburg effect in some cancer cells.In the present study we investigated gene expression profiles of key glycolytic enzymes and other proteins that respond to various metabolic stresses in liver from L‐PDCKO mice. Our findings indicate that (i) liver‐specific PDC deficiency is sufficient to induce ‘aerobic glycolysis characteristic’ in mouse liver, and (ii) the mechanism(s) responsible for these changes appears distinct from that which induces the Warburg effect in some cancer cells. [ABSTRACT FROM AUTHOR]

Dietary supplementation of α-lipoic acid, an 8-carbon organosulfur compound, has been widely reported to lower blood glucose concentration and/or improve insulin sensitivity in previous randomized controlled trials. Although animal model studies further report fairly consistent lipid lowering in both blood and tissue pools in response to α-lipoic acid supplementation, results from human studies are mixed. According to PRISMA guidelines, we conducted a systematic review of published randomized controlled studies (RCTs) to assess the efficacy of α-lipoic acid supplementation as a strategy to improve dyslipidemia, with a focus on serum lipid endpoints including TC, low density lipoprotein cholesterol (LDL-C), HDL-C, and TG. PubMed, EMBASE, Cochrane Evidence-Based Medicine Reviews, Proquest, Web of Science, and Scopus were searched to identify RCTs that reported the effects of α-lipoic acid on blood lipid concentrations from 1970 to 2017. We included RCTs reporting blood lipid responses in adults supplemented with oral α-lipoic acid versus a placebo or control for at least one month. Studies were reviewed and data were extracted by two independent study authors. Seventeen studies were deemed eligible for inclusion. Overall, mean percent changes in blood lipid endpoints in response to α-lipoic acid varied considerably between studies for total cholesterol (–10.5 to +13.9), low-density lipoprotein cholesterol (–19.67 to +9.06), high-density lipoprotein cholesterol (–12.5 to +29.20), and triglycerides (–38.57 to +17.0). Results of this systematic review suggest little consistent benefit on serum lipids in response to α-lipoic acid supplementation. Further well-controlled studies designed and powered to detect improvements in blood lipids in hypercholesterolemic individuals are warranted (PROSPERO registration number: CRD42018105933). [ABSTRACT FROM AUTHOR]

Maternal hypercholesterolemia (MHC) is a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during gestation, which can alter offspring hepatic lipid metabolism. However, the extent that these maladaptations occur during gestation and the molecular mechanisms involved remain unknown. MicoRNAs (miRNA) are small, noncoding RNAs that contribute to the development and progression of nonalcoholic fatty liver disease. Therefore, we sought to determine the degree to which in utero exposure to excessive cholesterol affects fetal hepatic lipid metabolism and miRNA expression. Twelve female apoE-/- mice were randomly assigned to two different chow-based diets throughout gestation: control (CON) or the CON diet with cholesterol (0.15%). MHC reduced maternal fecundity and reduced litter size and weight. On gestational day 18, fetuses from MHC dams possessed increased placental cholesterol and hepatic triglycerides (TG), which were accompanied by a downregulation in the expression of hepatic lipogenic and TG synthesis and transport genes. Furthermore, fetal livers from MHC mothers showed increased miRNA-27a and reduced miRNA-200c expression. In summary, in utero exposure to MHC alters fetal lipid metabolism and lends mechanistic insight that implicates early changes in miRNA expression that may link to later-life programming of disease risk. [ABSTRACT FROM AUTHOR]

Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking. [ABSTRACT FROM AUTHOR]

In hypercholesterolemic pregnancies, the maternal environment is characterized by excessive levels of atherogenic lipids that may increase cardiovascular disease risk in mothers and their offspring. We examined the influence of maternal hypercholesterolemia and phytosterol (PS) intervention on the concentration and metabolism of oxysterols, bioactive oxygenated cholesterol derivatives that regulate arterial health and lesion progression, in mothers and their newly weaned offspring. Twenty-one female apoE-/- mice were randomly assigned to three different diets throughout gestation and lactation: (1) chow, (2) high cholesterol (CH; 0.15%) and (3) CH with added PS (2%, CH/PS). At the end of the lactation period, mothers and pups were euthanized for serum and hepatic oxysterol analyses, hepatic transcriptional profiling of hepatic sterol regulatory targets and atherosclerosis. Hypercholesterolemic dams and their pups demonstrated increased (P˂.05) serum oxysterols [including 24 hydroxycholesterol (HC), 25HC, 27HC, 7αHC, 7βHC and 7 ketocholesterol)] compared with the chow group that were normalized by maternal PS supplementation. Hepatic oxysterol concentrations followed a similar pattern of response in mothers but were not altered in newly weaned pups. Hepatic mRNA expression suggested a pattern of enhanced abca1/g1 high-density-lipoprotein-mediated efflux but a reduction in biliary abcg5/g8 export in both dams and their pups. Although arterial lesions were not apparent in newly weaned pups, CH dams demonstrated enhanced atherosclerosis that was reduced upon PS intervention. These results demonstrate that offspring from hypercholesterolemic pregnancies have enhanced circulating oxysterol concentrations and highlight the potential utility of PS as a lipid-lowering option during hypercholesterolemic pregnancies for which there are currently limited options. [ABSTRACT FROM AUTHOR]

Objective: An excessive rise in blood lipids during pregnancy may promote metabolic dysfunction in adult progeny. We characterized how maternal phytosterol (PS) supplementation affected serum lipids and the expression of lipid-regulatory genes in the intestine and liver of newly-weaned apo-E deficient offspring from dams fed a chow diet supplemented with cholesterol (0.15%, CH) or cholesterol and PS (2%) (CH/PS) throughout pregnancy and lactation. Results: Serum lipid concentrations and lipoprotein particle numbers were exacerbated in offspring from cholesterol- supplemented mothers but normalized to chow-fed levels in pups exposed to PS through the maternal diet during gestation and lactation. Compared with the CH pups, pups from PS-supplemented mothers demonstrated higher (p < 0.05) expression of the primary intestinal cholesterol transport protein (Niemann-Pick C1-like 1) and the rate-limiting enzyme in hepatic cholesterol synthesis (HMG-CoAr), suggestive of a compensatory response to restore cholesterol balance. Furthermore, pups from PS-supplemented mothers exhibited a coordinated downregulation (p < 0.05) of several genes regulating fatty acid synthesis including PGC1β, SREBP1c, FAS, and ACC compared with the CH group. These results suggest that maternal PS supplementation during hypercholesterolemic pregnancies protects against aberrant lipid responses in newly-weaned offspring and results in differential regulation of cholesterol and lipid regulatory targets within the enterohepatic loop. [ABSTRACT FROM AUTHOR]

Purpose: We tested the hypothesis that elevations in biomarkers of acute kidney injury are influenced by the magnitude of hyperthermia and dehydration elicited by two common firefighter work durations. Methods: Twenty-nine healthy adults (10 females) wearing firefighter protective clothing completed two randomized trials where they walked at 4.8 km⋅h-1, 5% grade in a 38°C, 50% RH environment. In the short trial, subjects completed two 20-min exercise bouts. In the long trial (LONG), subjects completed three 20-min exercise bouts. Each exercise bout was separated by 10 min of standing rest in an ~20°C environment. Venous blood samples were obtained before and immediately after exercise, and after 1 h recovery. Dependent variables included changes in core temperature, body weight, plasma volume, serum creatinine, and plasma neutrophil gelatinase-associated lipocalin, a marker of renal tubule injury. Results: Changes in core temperature (+2.0°C ± 0.7°C vs +1.1 °C ± 0.4°C, P < 0.01), body weight (-0.9% ± 0.6% vs -0.5% ± 0.5%, P < 0.01), and plasma volume (-11% ± 5% vs -8% ± 6%, P < 0.01) during exercise were greater in LONG. Increases in creatinine were higher in LONG postexercise (0.18 ± 0.15 vs 0.08 ± 0.07 mg⋅dL-1, P < 0.01) and after recovery (0.21 ± 0.16 vs 0.14 ± 0.10 mg⋅dL-1, P < 0.01). Increases in neutrophil gelatinase-associated lipocalin were greater in LONG postexercise (27.0 ± 20.5 vs 12.7 ± 18.0 ng⋅mL-1, P = 0.01) and after recovery (16.9 ± 15.6 vs 1.5 ± 15.1 ng⋅mL-1, P = 0.02). Conclusions: Biomarkers of acute kidney injury are influenced by the magnitude of hyperthermia and hypovolemia elicited by exercise in the heat. [ABSTRACT FROM AUTHOR]

Background: Oxysterols are promising biomarkers of neurodegenerative diseases that are linked with cholesterol and vitamin D metabolism. There is an unmet need for methods capable of sensitive, and simultaneous quantitation of multiple oxysterols, vitamin D and cholesterol pathway biomarkers. Methods: A method for simultaneous determination of 5 major oxysterols, 25-hydroxy vitamin D3 and cholesterol in human plasma was developed. Total oxysterols were prepared by room temperature saponification followed by solid phase extraction from plasma spiked with deuterated internal standards. Oxysterols were resolved by reverse phase HPLC using a methanol/water/0.1% formic acid gradient. Oxysterols and 25-hydroxy vitamin D3 were detected with atmospheric pressure chemical ionization mass spectrometry in positive ion mode; in-series photodiode array detection at 204nm was used for cholesterol. Method validation studies were performed. Oxysterol levels in 220 plasma samples from healthy control subjects, multiple sclerosis and other neurological disorders patients were quantitated. Results: Our method quantitated 5 oxysterols, cholesterol and 25-hydroxy vitamin D3 from 200 μL plasma in 35 minutes. Recoveries were >85% for all analytes and internal standards. The limits of detection were 3-10 ng/mL for oxysterols and 25-hydroxy vitamin D3 and 1 μg/mL for simultaneous detection of cholesterol. Analytical imprecision was <10 %CV for 24(S)-, 25-, 27-, 7α-hydroxycholesterol (HC) and cholesterol and ≤15 % for 7-keto-cholesterol. Multiple Sclerosis and other neurological disorder patients had lower 27-hydroxycholesterol levels compared to controls whereas 7α-hydroxycholesterol was lower specifically in Multiple Sclerosis. Conclusion: The method is suitable for measuring plasma oxysterols levels in human health and disease. Analysis of human plasma indicates that the oxysterol, bile acid precursors 7α-hydroxycholesterol and 27-hydroxycholesterol are lower in Multiple Sclerosis and may serve as potential biomarkers of disease. [ABSTRACT FROM AUTHOR]

Background: High carbohydrate feeding is known to increase plasma triglycerides as well as hepatic de novo lipogenesis (DNL) and may be implicated in the development of hepatic insulin resistance and fatty liver. Unfortunately, it is technically challenging to determine what proportion of circulating plasma triglycerides have been derived from the newly synthesized fatty acids in the postprandial period. The aims of this study were to 1) characterize the changes in the plasma postprandial total fatty acid pool in beagles following the consumption of meals containing 44% (Control) and 74% (High Sucrose) carbohydrate and 2) determine if changes in plasma fatty acid concentration and delta-9 desaturation index (DI) would be useful as simple and easy to measure biomarkers of systemic DNL. Findings: No differences in plasma total palmitic acid (16:0), stearic acid (18:0) and oleic acid (18:1) concentrations or delta-9 DI for the total 18:0 and 18:1 pools between High Sucrose and Controls were observed. However, newly synthesized 16:0 (2.6 ± 0.2% vs. 8.8 ± 2.0%; p = 0.016), 18:0 (0.93 ± 0.2% vs. 4.1 ± 1.7%; p = 0.007) and 18:1 (0.29 ± 0.09% vs. 3.5 ± 1.2%; p = 0.017) were higher in High Sucrose versus Control animals, respectively. Also, the delta-9 DI for the newly synthesized 18:0 and 18:1 pools was higher at 2 and 6 hours postprandial, with a pattern of change which supports the increased stearoyl-CoA desaturase (SCD-1) activity following high carbohydrate feeding followed by a down regulation of this enzyme. Conclusions: Our data show that high sucrose meals increase the relative contribution of systemic DNL produced fatty acids to the total postprandial plasma fatty acid pool. These data also show that a different pattern of both fatty acid synthesis and disposal occurs depending on energy and macronutrient profile of the meal. These changes are in spite of no observable changes in the plasma concentrations or ratios of the total fatty acid pool opposed to the observed changes in the newly synthesized fatty acid pool. [ABSTRACT FROM AUTHOR]

We characterized the hypolipidemic effects of alpha-lipoic acid (LA, R-form) and examined the associated molecular mechanisms in a high fat fed Zucker rat model. Rats (n = 8) were assigned to a high fat (HF) diet or the HF diet with 0.25% LA (HF-LA) for 30 days and pair fed to remove confounding effects associated with the anorectic properties of LA. Compared with the HF controls, the HF-LA group was protected against diet-induced obesity (102.5±3.1 vs. 121.5±3.6,% change BW) and hypercholesterolemia with a reduction in total-C (−21%), non-HDL-C (−25%), LDL-C (−16%), and total LDL particle number (−46%) and an increase in total HDL particles (∼22%). This cholesterol-lowering response was associated with a reduction in plasma PCSK9 concentration (−70%) and an increase in hepatic LDLr receptor protein abundance (2 fold of HF). Compared with the HF-fed animals, livers of LA-supplemented animals were protected against TG accumulation (−46%), likely through multiple mechanisms including: a suppressed lipogenic response (down-regulation of hepatic acetyl-CoA carboxylase and fatty acid synthase expression); enhanced hepatic fat oxidation (increased carnitine palmitoyltransferase Iα expression); and enhanced VLDL export (increased hepatic diacylglycerol acyltransferase and microsomal triglyceride transfer protein expression and elevated plasma VLDL particle number). Study results also support an enhanced fatty acid uptake (2.8 fold increase in total lipase activity) and oxidation (increased CPT1β protein abundance) in muscle tissue in LA-supplemented animals compared with the HF group. In summary, in the absence of a change in caloric intake, LA was effective in protecting against hypercholesterolemia and hepatic fat accumulation under conditions of strong genetic and dietary predisposition toward obesity and dyslipidemia. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel biomarker of LDL clearance and a therapeutic target of cardiovascular disease. We examined the effects of aerobic exercise training in modulating PCSK9 abundance and hepatic sterol regulation in high-fat-fed C57BL/6 mice. Mice (n = 8) were assigned to a low-fat (LF), high-fat (HF), or an HF with exercise (HF + EX) group for 8 weeks. The HF + EX group was progressively trained 5 days/week on a motorized treadmill. The HF + EX group was protected against body weight (BW) gain and diet-induced dyslipidemia compared with the HF group. The HF + EX group demonstrated an increase in hepatic PCSK9 mRNA (1.9-fold of HF control, P < 0.05) and a reduction in plasma PCSK9 (14%) compared with the HF group. Compared with HF mice, HF + EX mice demonstrated reduced hepatic cholesterol (14%) and increased (P < 0.05 ) nuclear SREBP2 protein (1.8-fold of HF group) and LDLr mRNA (1.4-fold of HF group). Plasma PCSK9 concentrations correlated positively with plasma non-HDL-C (P = 0.01, r = 0.84). Results suggest that treadmill exercise reduces non-HDL cholesterol and differentially modulates hepatic and blood PCSK9 abundance in HF-fed C57BL/6 mice. [ABSTRACT FROM AUTHOR]

The objective was to evaluate the effects of whole and fractionated yellow peas on circulating lipids, glucose and insulin levels, energy expenditure, and body composition, as well as to assess their prebiotic actions in Golden Syrian hamsters. Forty-five hamsters consumed a hypercholesterolemic diet for 28 days, then were randomly assigned to 1 of 3 groups: control (CON), whole pea flour (WPF), and fractionated pea flour (hulls only) (FPF). WPF and FPF were incorporated into the diets, replacing 10% of the cornstarch. WPF and FPF feeding produced negligible effects on circulating cholesterol and triglyceride levels. However, both WPF (56.76 ± 9.22 pmol·L-1, p = 0.002) and FPF (89.27 ± 19.82 pmol·L-1, p = 0.032) reduced circulating insulin levels compared with the CON group (131.70 ± 17.70 pmol·L-1). Moreover, FPF decreased (p = 0.03) circulating glucose levels (6.26 ± 0.51 mmol·L-1) compared with CON (8.27 ± 0.81 mmol·L-1). Energy expenditure analysis revealed that hamsters consuming WPF demonstrated a higher (p = 0.036) oxygen consumption (2.00 ± 0.31 mL O2·g-1 lean body mass) vs. the CON group (1.56 ± 0.089 mL O2·g-1 lean body mass). Analysis of caecal digesta showed that WPF produced shifts in the abundance of microbial taxa with the most predominant changes occurring within the phylum Firmicutes. Yellow peas and their constituents should be investigated as future functional food ingredients that help prevent and manage lifestyle-related diseases such as diabetes and obesity. [ABSTRACT FROM AUTHOR]

Abstract: Background: Information is scarce regarding the effect of dietary protein type, with specific focus on the lysine-to-arginine (Lys:Arg) ratio, on cardiovascular risk factors and vascular reactivity in humans. Objective: Determine the effect of dietary Lys:Arg ratio on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults. Design: Randomized cross-over design of two 35-day diet phases; thirty adults (21 females and 9 males, ≥50 years, LDL cholesterol ≥120mg/dL). Diets had 20% energy (E) protein, 30%E fat, 50%E carbohydrate and were designed to have low (0.7) or high (1.4) Lys:Arg ratio. Measures included fasting and postprandial lipid, lipoprotein, apolipoprotein concentrations; fasting high sensitivity C-reactive protein (hsCRP), small dense LDL (sdLDL) cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities; cholesterol fractional synthesis rate (FSR); and flow mediated dilation (FMD) and peripheral artery tonometry (PAT). Results: No differences were observed in fasting and/or postprandial total, LDL, HDL and sdLDL cholesterol, RemLC, Lp(a) or apo B concentrations, LCAT and CETP activities, FSR, glycated albumin, immunoreactive insulin, FMD or PAT. The low, relative to the high, Lys:Arg ratio diet resulted in lower postprandial VLDL cholesterol (−24%, P =0.001) and triglycerides (−23%, P =0.001), and small but significant differences in fasting (−3%, P =0.003) and postprandial (−3%, P =0.018) apo AI, and fasting adiponectin concentrations (+7%, P =0.035). Fasting and postprandial hsCRP concentrations were 23% lower after the low Lys:Arg ratio diet (P =0.020 for both). Conclusions: Diets differing in Lys:Arg ratios had no or small effects on cardiovascular risk factors and vascular reactivity. [Copyright &y& Elsevier]

Diacyiglycerol (DAG) may undergo differential metabolism compared with triacylglycerol (TAG) in humans, possibly resulting in decreased serum TAG concentration and TAG synthesis and increased energy expenditure (EEl, thus reducing fat accumulation. Our objective was to examine the efficacy of DAG oil )Enova oil) consumption on serum lipid profiles, hepatic lipogenesis, EE, and body weight and composition compared with a control oil-blend composed of sunflower, safflower, and rapeseed oils at a 1:1:1 ratio. Twenty-six overweight (78.3 ± 3.6 kg body weight and BM) 30.0 ± 0.7 kg/rn2) mildly hypertriglyceridemic 11.81 ± 0.66 rnmol/L) women underwent 2 treatment phases of 28 d separated by a 4-wk washout period using a randomized crossover design. They consumed 40 g/d of either DAG or control oil during treatment phases. The baseline, EE, fat oxidation, body composition, and lipid profiles did not differ between the DAG and control oil intervention periods. Relative to control oil, DAG oil did not alter endpoint postprandial EE, fat oxidation, serum lipid profiles, or hepatic lipogenesis. However, DAG oil consumption reduced (P < 0.05) accumulation of body fat within trunk, android, and gynoid regions at the endpoint compared with control oil, although neither DAG nor control oil altered any of these variables during the 4-wk intervention period compared with their respective baseline levels. We conclude that although DAG oil is not effective in lowing serum lipids over a 4-wk intervention, it may be useful for reducing adiposity. [ABSTRACT FROM AUTHOR]

Fractional protein synthesis rates (FSR) are widely measured by the flooding dose technique via either an i.g. or an i.v. route. This study was conducted to compare differences in tracer incorporation and FSR in organs and tissues of fed piglets. The piglets were surgically implanted with catheters and randomly assigned to receive a flooding dose of Phe (1.5 mmol/kg body weight, 40 percent molar enrichment with [(2)H(5)]Phe) in saline administered via an i.p. or an i.v. route. [(2)H(5)]Phe free-pool enrichment in plasma increased logarithmically (P < 0.05) from 0 to 25% in the i.p. group, whereas it rose to a peak level within 3 min of the tracer injection and then decreased linearly (P < 0.05) in the i.v. group. Intracellular free-pool tracer enrichments in organs and tissues were within the range of the values measured for the plasma-free pool (25-27%), reaching the flooding status. Administration of the tracer via the i.p. and i.v. routes induced a logarithmical pattern (P < 0.05) of a surge in plasma cortisol concentrations within 30 min. Measurements of FSR in plasma, cardiac muscle, and skeletal muscles were lower (P < 0.05) in the i.p. than in the i.v. group due to the adverse effect of cortisol surge being more dramatic (P < 0.05) in the i.p. than in the i.v. group at 30 min of the post-tracer administration. We conclude that FSR may be measured by the flooding dose through an i.p. or an i.v. route and the i.p. route may underestimate FSR by the flooding dose for plasma, cardiac muscle, and skeletal muscles. This concern may be addressed by a fast regimen of sampling to be completed within 12-20 min after an i.p. route of tracer injection. [ABSTRACT FROM AUTHOR]

Fractional protein synthesis rates (FSR) are widely measured by the flooding dose technique via either an i.g. or an iv. route. This study was conducted to compare differences in tracer incorporation and FSR in organs and tissues of fed piglets. The piglets were surgically implanted with catheters and randomly assigned to receive a flooding dose of Phe 11.5 mmol/kg body weight, 40 percent molar enrichment with [2H5]Phe) in saline administered via an i.p. or an i.v. route. [2H5]Phe free-pool enrichment in plasma increased logarithmically (P < 0.05) from 0 to 25% in the i.p. group, whereas it rose to a peak level within 3 mm of the tracer injection and then decreased linearly (P < 0.05) in the iv. group. Intracellular free-pool tracer enrichments in organs and tissues were within the range of the values measured for the plasma-free pool (25-27%), reaching the flooding status. Administration of the tracer via the i.p. and iv. routes induced a logarithmical pattern (P < 0.05) of a surge in plasma cortisol concentrations within 30 mm. Measurements of FSR in plasma, cardiac muscle, and skeletal muscles were lower (P < 0.05) in the i.p. than in the i.v. group due to the adverse effect of cortisol surge being more dramatic (P < 0.05) in the i.p. than in the iv. group at 30 mm of the post-tracer administration. We conclude that FSR may be measured by the flooding dose through an i.p. or an i.v. route and the i.p. route may underestimate FSR by the flooding dose for plasma, cardiac muscle, and skeletal muscles. This concern may be addressed by a fast regimen of sampling to be completed within 12-20 mm after an i.p. route of tracer injection. [ABSTRACT FROM AUTHOR]