Metabolic responses to food influence risk of cardiometabolic disease, but large-scale high-resolution studies are lacking. We recruited n = 1,002 twins and unrelated healthy adults in the United Kingdom to the PREDICT 1 study and assessed postprandial metabolic responses in a clinical setting and at home. We observed large inter-individual variability (as measured by the population coefficient of variation (s.d./mean, %)) in postprandial responses of blood triglyceride (103%), glucose (68%) and insulin (59%) following identical meals. Person-specific factors, such as gut microbiome, had a greater influence (7.1% of variance) than did meal macronutrients (3.6%) for postprandial lipemia, but not for postprandial glycemia (6.0% and 15.4%, respectively); genetic variants had a modest impact on predictions (9.5% for glucose, 0.8% for triglyceride, 0.2% for C-peptide). Findings were independently validated in a US cohort (n = 100 people). We developed a machine-learning model that predicted both triglyceride (r = 0.47) and glycemic (r = 0.77) responses to food intake. These findings may be informative for developing personalized diet strategies. The ClinicalTrials.gov registration identifier is NCT03479866.

/pdf/human-postprandial-responses-to-food-and-potential-for-3djywagsis.pdf

Human postprandial responses to food and potential for precision nutrition.

BACKGROUNDDietary changes have led to the growing prevalence of type 2 diabetes and nonalcoholic fatty liver disease. A hallmark of both disorders is hepatic lipid accumulation, derived in part from increased de novo lipogenesis. Despite the popularity of high-protein diets for weight loss, the effect of dietary protein on de novo lipogenesis is poorly studied. We aimed to characterize the effect of dietary protein on de novo lipid synthesis.METHODSWe use a 3-way crossover interventional study in healthy males to determine the effect of high-protein feeding on de novo lipogenesis, combined with in vitro models to determine the lipogenic effects of specific amino acids. The primary outcome was a change in de novo lipogenesis-associated triglycerides in response to protein feeding.RESULTSWe demonstrate that high-protein feeding, rich in glutamate, increases de novo lipogenesis-associated triglycerides in plasma (1.5-fold compared with control; P < 0.0001) and liver-derived very low-density lipoprotein particles (1.8-fold; P < 0.0001) in samples from human subjects (n = 9 per group). In hepatocytes, we show that glutamate-derived carbon is incorporated into triglycerides via palmitate. In addition, supplementation with glutamate, glutamine, and leucine, but not lysine, increased triglyceride synthesis and decreased glucose uptake. Glutamate, glutamine, and leucine increased activation of protein kinase B, suggesting that induction of de novo lipogenesis occurs via the insulin signaling cascade.CONCLUSIONThese findings provide mechanistic insight into how select amino acids induce de novo lipogenesis and insulin resistance, suggesting that high-protein feeding to tackle diabetes and obesity requires greater consideration.FUNDINGThe research was supported by UK Medical Research Council grants MR/P011705/1, MC_UP_A090_1006 and MR/P01836X/1. JLG is supported by the Imperial Biomedical Research Centre, National Institute for Health Research (NIHR).

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A randomized 3-way crossover study indicates that high-protein feeding induces de novo lipogenesis in healthy humans

Purpose
Evolocumab significantly reduces low-density lipoprotein-cholesterol (LDL-C); we investigated its effects on LDL-C lowering in patients with mixed hyperlipidemia.

/pdf/efficacy-and-safety-of-the-pcsk9-inhibitor-evolocumab-in-1ala1l554m.pdf

Efficacy and Safety of the PCSK9 Inhibitor Evolocumab in Patients with Mixed Hyperlipidemia

Majority of studies that focused on the influence of abdominal obesity on lipoprotein profile, were conducted in the fasting conditions. The effects of visceral fat accumulation on postprandial lipoprotein concentrations have not yet been studied in details. We therefore focused on the postprandial lipoprotein profile in otherwise healthy men and women with abdominal obesity and their comparison with the control group of volunteers with normal waist circumference. The concentration of lipoprotein classes and subclasses was measured before and 4 hours after a standard meal by linear polyacrylamide gel electrophoresis. A statistically significant postprandial rise in triacylglycerol concentration occurred in all subjects. VLDL increased 4 hours after meal in all subjects except the women with normal waist circumference. The concentration of large IDL particles increased in both non-obese men and women. In women with abdominal obesity, however, it decreased, while in obese men there was no statistically significant change. The concentration of small and medium-sized IDL particles decreased in all volunteers. Analyzing subclasses changes of large, medium-sized and small LDL particles we saw no significant shift in their concentrations except the subclass of large LDL particles, which decreased in men. Concentrations of medium and small HDL particles decreased postprandially in all volunteers with normal waist circumference. However, they remained unchanged in subjects with abdominal obesity. We observed significant postprandial changes of the lipoprotein profile, but the nature and extent of these changes depended on gender and presence of abdominal obesity.

/pdf/postprandial-changes-of-lipoprotein-profile-effect-of-2935r438os.pdf

Postprandial changes of lipoprotein profile: effect of abdominal obesity

Maintaining total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)and triglyceride (TG) levels within healthy limits decreases the risk of atherosclerotic vascular disease (AVD) and cardiovascular (CV)events. The predictive value of elevated TG levels for coronary artery disease (CAD) seen in univariate analysis tends to disappear onmultivariate analyses, especially when correction is made for HDL-C.The relationship between TG and HDL-C is complex and not fully understood. Hydrolysis of TG by lipoprotein lipase converts HDLsubclass 3 to a larger lipoprotein enriched in both phospholipid and TG. This process occurs in postprandial lipaemia (PPL). An additionalfactor for the complex relationship between TGs and CV risk is that the lipoproteins which transport plasma TG (chylomicrons,very low density lipoproteins and their remnants) are heterogeneous particles. Therefore, they may differ in their level of atherogenicity.PPL is a physiological process during which plasma lipoproteins and their subclasses undergo variations in concentration and compositionfollowing consumption of food, particularly fatty food. “Postprandial hyperlipidaemia” is the quantitative/qualitative alteration ofthis normal process. These lipoprotein alterations could play a role in the development of CV disease (CVD). However, lipid levels usedto evaluate CV risk are usually measured in the fasting state.This review focuses on TG, PPL, postprandial hyperlipidaemia and non-HDL-C, their relationships and potential predictive role inatherogenesis and CVD.

Hypertriglyceridaemia, Postprandial Lipaemia and Non-HDL Cholesterol

Background
Dyslipidemia is associated with cardiovascular morbidities and mortality. Currently, fasting lipid profile determination is used to monitor treatment response. Recently, postprandial lipemia is of increasing interest because of its atherogenic and thrombogenic potential and also was found to be more predictive for cardiovascular diseases.

/pdf/postprandial-peaking-and-plateauing-of-triglycerides-and-3ac4zsk5je.pdf

Ana Lyza B. Galia

Papers

Postprandial Peaking and Plateauing of Triglycerides and VLDL in Patients with Underlying Cardiovascular Diseases Despite Treatment