We investigated the effects of eicosapentaenoic acid (EPA) on prevention (P) and reversal (R) of high saturated-fat (HF) diet-induced obesity and glucose-insulin homeostasis. Male C57BL/6J mice were fed low-fat (LF; 10% energy from fat), HF (45% energy from fat), or a HF-EPA-P (45% energy from fat; 36 g/kg EPA) diet for 11 wk. A 4th group was initially fed HF for 6 wk followed by the HF-EPA-R diet for 5 wk. As expected, mice fed the HF diet developed obesity and glucose intolerance. In contrast, mice fed the HF-EPA-P diet maintained normal glucose tolerance despite weight gain compared with the LF group. Whereas the HF group developed hyperglycemia and hyperinsulinemia, both HF-EPA groups (P and R) exhibited normal glycemia and insulinemia. Further, plasma adiponectin concentration was lower in the HF group but was comparable in the LF and HF-EPA groups, suggesting a role of EPA in preventing and improving insulin resistance induced by HF feeding. Further analysis of adipose tissue adipokine levels and proteomic studies in cultured adipocytes indicated that dietary EPA supplementation of HF diets was associated with reduced adipose inflammation and lipogenesis and elevated markers of fatty acid oxidation. In C57BL/6J mice, EPA minimized saturated fat-induced insulin resistance and this is in part mediated by its effects on fatty acid oxidation and inflammation.

Background Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low density lipoprotein cholesterol (LDL-C) and apolipoprotein B100 (apoB). Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism. In particular, it is not known if inhibition of PCSK9 has any effects on very low density lipoprotein (VLDL) or intermediate density lipoprotein (IDL) metabolism. Inhibition of PCSK9 also results in reductions of plasma Lp(a) levels. The regulation of plasma Lp(a) levels, including the role of LDL receptors (LDLRs) in the clearance of Lp(a), is poorly defined, and there have been no mechanistic studies of the Lp(a) lowering by alirocumab in humans. Methods Eighteen (10F, 8M) participants completed a placebo-controlled, two-period study. They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart. At the end of each period, fractional clearance rates (FCR) and production rates (PR) of apoB and apo(a) were determined. In 10 participants, postprandial triglycerides (TG) and apoB48 levels were measured. Results Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%. The fall in LDL-apoB was due to an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR. The latter was associated with a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL. The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR. Alirocumab had no effects on FCRs or PRs of VLDL-apoB and VLDL-TG, or on postprandial plasma TG or apoB48 concentrations. Conclusions Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs, and decreasing LDL-apoB PR. These results are consistent with increases in LDLRs available to clear IDL and LDL from blood during PCSK9 inhibition. The possible increase in apo(a) FCR during alirocumab treatment suggests that increased LDLRs may also play a role in the reduction of plasma Lp(a). Clinical Trials Registration Clinical trials.gov # NCT01959971

BackgroundEpidemiologic data suggest that diets rich in nuts have beneficial health effects, including reducing total and cause-specific mortality from cancer and heart disease. Although there is accumulating preclinical evidence that walnuts beneficially affect the gastrointestinal microbiota and gut and metabolic health, these relations have not been investigated in humans.ObjectiveWe aimed to assess the impact of walnut consumption on the human gastrointestinal microbiota and metabolic markers of health.MethodsA controlled-feeding, randomized crossover study was undertaken in healthy men and women [n = 18; mean age = 53.1 y; body mass index (kg/m2): 28.8]. Study participants received isocaloric diets containing 0 or 42 g walnuts/d for two 3-wk periods, with a 1-wk washout between diet periods. Fecal and blood samples were collected at baseline and at the end of each period to assess secondary outcomes of the study, including effects of walnut consumption on fecal microbiota and bile acids and metabolic markers of health.ResultsCompared with after the control period, walnut consumption resulted in a 49–160% higher relative abundance of Faecalibacterium, Clostridium, Dialister, and Roseburia and 16–38% lower relative abundances of Ruminococcus, Dorea, Oscillospira, and Bifidobacterium (P < 0.05). Fecal secondary bile acids, deoxycholic acid and lithocholic acid, were 25% and 45% lower, respectively, after the walnut treatment compared with the control treatment (P < 0.05). Serum LDL cholesterol and the noncholesterol sterol campesterol concentrations were 7% and 6% lower, respectively, after walnut consumption compared with after the control treatment (P < 0.01).ConclusionWalnut consumption affected the composition and function of the human gastrointestinal microbiota, increasing the relative abundances of Firmicutes species in butyrate-producing Clostridium clusters XIVa and IV, including Faecalibacterium and Roseburia, and reducing microbially derived, proinflammatory secondary bile acids and LDL cholesterol. These results suggest that the gastrointestinal microbiota may contribute to the underlying mechanisms of the beneficial health effects of walnut consumption. This trial was registered at www.clinicaltrials.gov as NCT01832909.

An elevated LDL-cholesterol concentration is a wellestablished independent risk factor for cardiovascular disease (CVD) ( 1 ). Large-scale primary and secondary prevention trials aimed at lowering plasma total and LDLcholesterol concentrations have resulted in marked reductions in CVD events and mortality ( 2-9 ). However, CVD events still occur in a substantial proportion of individuals not presenting with elevated LDL-cholesterol concentrations. Using the 90th percentile for age and sex according to the Lipid Research Clinics data for LDL-cholesterol and triglyceride concentrations and the 10th percentile for HDL-cholesterol, in patients with premature coronary artery disease (CAD), relative to matched control subjects, only 12% versus 9% had elevated LDL-cholesterol concentrations, 19% versus 4% had low HDL-cholesterol concentrations, and 10% versus 9% had elevated triglyceride concentrations ( 10 ). Based on the aforementioned criteria, 39% of patients with premature CAD had no conventional lipid abnormality. Similarly, data from several clinical trials suggest that although LDL-cholesterol lowering was highly effi cacious, the reduction in the relative risk of major coronary events was poorly associated with baseline serum lipid concentrations ( 2-6, 8, 9, 11 ). Abstract

Objectives-Extended-release niacin effectively lowers plasma TG levels and raises plasma high-density lipoprotein (HDL) cholesterol levels, but the mechanisms responsible for these effects are unclear. Methods and Results-We examined the effects of extended-release niacin (2 g/d) and extended-release niacin (2 g/d) plus lovastatin (40 mg/d), relative to placebo, on the kinetics of apolipoprotein (apo) A-I and apoA-II in HDL, apoB-100 in TG-rich lipoproteins (TRL), intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), and apoB-48 in TRL in 5 men with combined hyperlipidemia. Niacin significantly increased HDL cholesterol and apoA-I concentrations, associated with a significant increase in apoA-I production rate (PR) and no change in fractional catabolic rate (FCR). Plasma TRL apoB-100 levels were significantly lowered by niacin, accompanied by a trend toward an increase in FCR and no change in PR. Niacin treatment significantly increased TRL apoB-48 FCR but had no effect on apoB-48 PR. No effects of niacin on concentrations or kinetic parameters of IDL and LDL apoB-100 and HDL apoA-II were noted. The addition of lovastatin to niacin promoted a lowering in LDL apoB-100 attributable to increased LDL apoB-100 FCR. Conclusion-Niacin treatment was associated with significant increases in HDL apoA-I concentrations and production, as well as enhanced clearance of TRL apoB-100 and apoB-48. Key Words: apolipoprotein Ⅲ high-density lipoprotein Ⅲ kinetics Ⅲ lipid-lowering medications Ⅲ triglyceride T he cholesterol-lowering effect of the vitamin nicotinic acid, or niacin, was first reported by Altschul et al 1 more than 50 years ago. Since then, treatment with pharmacological doses of niacin has been found to significantly lower the risk of coronary heart disease (CHD). 2,3 Several trials have also tested the effect of niacin in combination with other lipid-lowering medications on CHD risk, overall showing a beneficial effect. 4 -6 Niacin primarily decreases plasma triglyceride (TG) levels and very low-density lipoprotein (VLDL) cholesterol (C) levels and increases plasma highdensity lipoprotein (HDL)-C levels. 2,7 It has been hypothesized that the reduction in TG and VLDL-C is mediated by the niacin-associated inhibition of free-fatty acid (FFA) release from the adipose tissue, which may lead to reduced substrate availability for TG synthesis and secretion in hepatic cells. 8 However, a study conducted in 1 hypertriglyceridemic subject showed faster clearance of autologous 125 Ilabeled VLDL after niacin treatment. 9 Niacin is one of the most potent HDL-C-raising agents currently available. Two previous studies have attempted to elucidate the effect of niacin on HDL metabolism in young normocholesterolemic subjects. 10,11 The first study was conducted in 2 subjects and found an increase in HDL-C levels associated with a slower HDL catabolism with niacin. 10 The second study, in 5 young healthy subjects, found a significant increase in plasma HDL-C and apolipoprotein (apo) A-I levels with niacin withou...

OBJECTIVE To determine the impact of maternal obesity on breastmilk composition. STUDY DESIGN Breastmilk and food records from 21 lean and 21 obese women who delivered full-term infants were analyzed at 2 months post-partum. Infant growth and adiposity were measured at birth and 2 months of age. RESULT Breastmilk from obese mothers had higher omega-6 to omega-3 fatty acid ratio and lower concentrations of docosahexaenoic acid, eicosapentaenoic acid, docasapentaenoic acid and lutein compared with lean mothers (P < 0.05), which were strongly associated with maternal body mass index. Breastmilk saturated fatty acid and monounsaturated fatty acid concentrations were positively associated with maternal dietary inflammation, as measured by dietary inflammatory index. There were no differences in infant growth measurements. CONCLUSION Breastmilk from obese mothers has a pro-inflammatory fatty acid profile and decreased concentrations of fatty acids and carotenoids that have been shown to have a critical role in early visual and neurodevelopment. Studies are needed to determine the link between these early-life influences and subsequent cardiometabolic and neurodevelopmental outcomes.

Background: The utility of glycemic index (GI) values for chronic disease risk management remains controversial. Although absolute GI value determinations for individual foods have been shown to vary significantly in individuals with diabetes, there is a dearth of data on the reliability of GI value determinations and potential sources of variability among healthy adults. Objective: We examined the intra-and inter-individual variability in glycemic response to a single food challenge and methodologic and biological factors that potentially mediate this response. Design: The GI value for white bread was determined by using standardized methodology in 63 volunteers free from chronic disease and recruited to differ by sex, age (18-85 y), and body mass index [BMI (in kg/m 2 ): 20-35]. Volunteers randomly underwent 3 sets of food challenges involving glucose (reference) and white bread (test food), both providing 50 g available carbohydrates. Serum glucose and insulin were monitored for 5 h postingestion, and GI values were calculated by using different area under the curve (AUC) methods. Biochemical variables were measured by using standard assays and body composition by dual-energy X-ray absorptiometry. Results: The mean 6 SD GI value for white bread was 62 6 15 when calculated by using the recommended method. Mean intraand interindividual CVs were 20% and 25%, respectively. Increasing sample size, replication of reference and test foods, and length of blood sampling, as well as AUC calculation method, did not improve the CVs. Among the biological factors assessed, insulin index and glycated hemoglobin values explained 15% and 16% of the variability in mean GI value for white bread, respectively. Conclusions: These data indicate that there is substantial variability in individual responses to GI value determinations, demonstrating that it is unlikely to be a good approach to guiding food choices. Additionally, even in healthy individuals, glycemic status significantly contributes to the variability in GI value estimates. This trial was registered at clinicaltrials.gov as NCT01023646.Am J Clin Nutr 2016;104:1004-13.

All varieties of soybean oils resulted in more favorable lipoprotein profiles than did the partially hydrogenated form. These soybean oils may provide a viable option for reformulation of products to reduce the content of trans fatty acids.