Prandial Hypertriglyceridemia in Metabolic Syndrome Is Due to an Overproduction of Both Chylomicron and VLDL Triacylglycerol

Abstract

The aim was to determine whether fed VLDL and chylomicron (CM) triacylglycerol (TAG) production rates are elevated in metabolic syndrome (MetS). Eight men with MetS (BMI 29.7 ± 1.1) and eight lean age-matched healthy men (BMI 23.1 ± 0.4) were studied using a frequent feeding protocol. After 4 h of feeding, an intravenous bolus of 2H5-glycerol was administered to label VLDL1, VLDL2, and TAG. 13C-glycerol tripalmitin was administered orally as an independent measure of CM TAG metabolism. Hepatic and intestinal lipoproteins were separated by an immunoaffinity method. In MetS, fed TAG and the increment in TAG from fasting to feeding were higher (P = 0.03 and P = 0.04, respectively) than in lean men. Fed CM, VLDL1, and VLDL2 TAG pool sizes were higher (P = 0.006, P = 0.03, and P < 0.02, respectively), and CM, VLDL1, and VLDL2 TAG production rates were higher (P < 0.002, P < 0.05, and P = 0.06, respectively) than in lean men. VLDL1, VLDL2, and CM TAG clearance rates were not different between groups. In conclusion, prandial hypertriglyceridemia in men with MetS was due to an increased production rate of both VLDL and CM TAG. Since both groups received identical meals, this suggests that in MetS the intestine is synthesizing more TAG de novo for export in CMs.

Liraglutide Reduces Postprandial Hyperlipidemia by Increasing ApoB48 (Apolipoprotein B48) Catabolism and by Reducing ApoB48 Production in Patients With Type 2 Diabetes Mellitus

“…1 It has been shown to be the result of an increase in chylomicron production 2 and a reduction in chylomicron clearance. 5 The increased chylomicron production, observed in type 2 diabetic patients, has been shown to be related to an increased rate of intestinal ApoB48 secretion 3 and an augmented expression of MTP within the intestine.…”

“…1 Patients with type 2 diabetes mellitus show an increase in chylomicron production 2 in conjunction with an increased rate of intestinal ApoB48 secretion 3 and an augmented expression of MTP (microsomal transfer protein; responsible for the addition of triglycerides to ApoB48 [apolipoprotein B48]) within the intestine. 4 In addition, the clearance of chylomicrons is impaired in type 2 diabetes mellitus.…”

Fasting Plasma Insulin Concentrations Are Associated With Changes in Hepatic Fatty Acid Synthesis and Partitioning Prior to Changes in Liver Fat Content in Healthy Adults

“…Although we did not measure VLDL-TG production rates, others (42,43) have reported VLDL apoB and TG production rates are higher in obese, insulin-resistant individuals compared with lean, insulin-sensitive individuals. In contrast, acute induction of hyperinsulinemia in healthy insulin-sensitive men suppresses the total production rate of VLDL apoB and TG (44), even in the presence of excess NEFA concentrations (45).…”

Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones

“…Interestingly, VLDL production and release are typically amplified in patients with NAFLD and the metabolic syndrome, contributing to hypertriglyceridemia and extrahepatic lipid uptake (Shojaee-Moradie et al 2013). Glucagon, cortisol and growth hormone stimulate hepatic VLDL secretion, while norepinephrine inhibits secretion (Fig.…”