Postprandial lipemia, which is one of the main characteristics of the atherogenic dyslipidemia with fasting plasma hypertriglyceridemia, low high-density lipoprotein cholesterol and an increase of small and dense low-density lipoproteins is now considered a causal risk factor for atherosclerotic cardiovascular disease and all-cause mortality. Postprandial lipemia, which is mainly related to the increase in chylomicron production, is frequently elevated in individuals at high cardiovascular risk such as obese or overweight patients, type 2 diabetic patients and subjects with a metabolic syndrome who share an insulin resistant state. It is now well known that chylomicron production and thus postprandial lipemia is highly regulated by many factors such as endogenous factors: circulating factors such as hormones or free fatty acids, genetic variants, circadian rhythms, or exogenous factors: food components, dietary supplements and prescription drugs. In this review, we focused on the effect of nutrients, micronutrients and phytochemicals but also on food structure on chylomicron production and postprandial lipemia.

Objective—: The dyslipidemia of obesity and other insulin-resistant states is characterized by the elevation of plasma triglyceride-rich lipoproteins (TRL) of both hepatic (apoB-100–containing very low-density lipoprotein) and intestinal (apoB-48–containing chylomicrons) origin. Bariatric surgery is a well-established and effective modality for the treatment of obesity and is associated with improvements in several metabolic abnormalities associated with obesity, including a reduction in plasma triglycerides. Here, we have investigated the effect of bariatric surgery on TRL metabolism. Approach and Results—: Twenty-two nondiabetic, obese subjects undergoing bariatric surgery: sleeve gastrectomy (n=12) or gastric bypass (n=10) were studied. Each subject underwent 1 lipoprotein turnover study 1 month before surgery followed by a second study, 6 months after surgery, using established stable isotope enrichment methodology, in constant fed state. TRL-apoB-100 concentration was significantly reduced after sleeve gastrectomy, explained by a decrease ( P <0.05) in TRL-apoB-100 production rate and an increase ( P <0.05) in TRL-apoB-100 fractional catabolic rate. TRL-apoB-48 concentration was also significantly reduced after sleeve gastrectomy, explained by reduction in TRL-apoB-48 production rate ( P <0.05). For gastric bypass, although TRL-apoB-100 concentration declined after surgery ( P <0.01), without a significant decline in TRL-apoB-48, there was no significant change in either TRL-apoB-100 or TRL-apoB-48 production rate or fractional catabolic rate. The reduction in TRL-apoB-100 concentration was significantly associated with a reduction in plasma apoC-III in the pooled group of patients undergoing bariatric surgery. Conclusions—: This is the first human lipoprotein kinetic study to explore the mechanism of improvement of TRL metabolism after bariatric surgery. These effects may contribute to the decrease of cardiovascular mortality after surgery. Clinical Trial Registration—: URL: http://www.ClinicalTrials.gov . Unique identifier: NCT01277068.

BACKGROUND: Patients with homozygous familial hypercholesterolemia (HoFH) remain at very high cardiovascular risk despite the best standard of care lipid-lowering treatment. The addition of evinacumab, an angiopoietin-like protein 3 monoclonal antibody, more than halves low-density lipoprotein cholesterol in short-term studies. This study evaluated whether the evinacumab response was durable in the long term and improved cardiovascular outcome. METHODS: The OLE ELIPSE HoFH (Open-Label Extension to Evinacumab Lipid Studies in Patients With HoFH) study included newly diagnosed patients and those completing the ELIPSE HoFH trial, on stable lipid-lowering therapy including lipoprotein apheresis but not lomitapide. All patients received evinacumab (15 mg/kg intravenously) every 4 weeks, with no change in concomitant lipid-lowering treatment during the first 6 months. The primary efficacy end points were the mean absolute and percentage changes in low-density lipoprotein cholesterol from baseline to 6 months. A key secondary end point was cardiovascular event–free survival, which was compared with a control HoFH cohort not treated with evinacumab or lomitapide and matched for age, sex, and lipoprotein apheresis, derived from French Registry of Familial hypercholesterolemia. RESULTS: Twelve patients, 5 women and 7 men (12–57 years), were enrolled in 3 centers in France. At 6 months, the mean low-density lipoprotein cholesterol reduction with evinacumab was 3.7 mmol/L or 56% (from 6.5 mmol/L at baseline to 2.8 mmol/L; P <0.0001) and was sustained over the median 3.5-year follow-up. No patients on evinacumab experienced cardiovascular events versus 13 events for 5/21 (24%) over 4 years in the control cohort (likelihood P =0.0267). CONCLUSIONS: Real-life, long-term evinacumab adjunctive to lipid-lowering therapy including lipoprotein apheresis led to sustained low-density lipoprotein cholesterol lowering and improved cardiovascular event–free survival of patients with HoFH.

Dominant variants in WFS1 (wolframin ER transmembrane glycoprotein), the gene coding for a mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) resident protein, have been associated with Wolfram-like syndrome (WLS). In vitro and in vivo, WFS1 loss results in reduced ER to mitochondria calcium (Ca²⁺) transfer, mitochondrial dysfunction, and enhanced macroautophagy/autophagy and mitophagy. However, in the WLS pathological context, whether the mutant protein triggers the same cellular processes is unknown. Here, we show that in human fibroblasts and murine neuronal cultures the WLS protein WFS1^E864K leads to decreases in mitochondria bioenergetics and Ca²⁺ uptake, deregulation of the mitochondrial quality system mechanisms, and alteration of the autophagic flux. Moreover, in the Wfs1^E864K mouse, these alterations are concomitant with a decrease of MAM number. These findings reveal pathophysiological similarities between WS and WLS, highlighting the importance of WFS1 for MAM's integrity and functionality. It may open new treatment perspectives for patients with WLS.Abbreviations: BafA1: bafilomycin A₁; ER: endoplasmic reticulum; HSPA9/GRP75: heat shock protein family A (Hsp70) member 9; ITPR/IP₃R: inositol 1,4,5-trisphosphate receptor; MAM: mitochondria-associated endoplasmic reticulum membrane; MCU: mitochondrial calcium uniporter; MFN2: mitofusin 2; OCR: oxygen consumption rate; ROS: reactive oxygen species; ROT/AA: rotenone+antimycin A; VDAC1: voltage dependent anion channel 1; WLS: Wolfram-like syndrome; WS: Wolfram syndrome; WT: wild-type.

The growth hormone (GH)–insulin-like growth factor-1 (IGF-1) axis is dramatically altered in patients with anorexia nervosa (AN). The aim of the present study was to investigate whether GH and IGF-1 could be predictors of outcome in patients with a restrictive form of AN. Blood levels of GH, IGF-1, adipocytokines, ghrelin, insulin, glucose, and sex and thyroid hormones were measured in eleven women inpatients with AN and in ten healthy women controls. Three stages were compared during refeeding: admission (T0), when BMI reached 16 kg/m² (T1) and at discharge when BMI reached 17·5 kg/m² (T2). Clinical status was assessed 6 months after discharge from hospital (T3), and remission was defined by the maintenance of a BMI ≥ 17·5 kg/m². AN patients in remission (AN-R; n 6) had significantly higher GH levels at admission than those who relapsed (AN-NR; n 5) (P< 0·05). During refeeding (Δ = T2 − T0), the AN-R group differed from the AN-NR group only by both GH level decrease (P< 0·05) and BMI increase (P< 0·05). In multiple regression analysis, ΔGH was associated negatively and significantly and Δleptin and Δbody fat mass levels were associated positively and significantly with BMI at T3 and explained 88 % of its variability (r² 0·88, P< 0·05). The present study suggests that a low GH level at admission and the absence of its decrease after weight recovery could predict short-term relapse in women suffering from a restrictive form of AN.