One day of mixed meal overfeeding reduces hepatic insulin sensitivity and increases VLDL particle but not VLDL-triglyceride secretion in overweight and obese men

Abstract

Context: The exact mechanisms responsible for increased plasma triglyceride (TG) concentration in obese people are unclear, and it is not known whether excess energy intake per se is involved in the pathophysiology of this abnormality.

Objective: The purpose of our study was to examine how excess energy intake from a balanced diet for 1 day affects very-low-density lipoprotein (VLDL)-TG kinetics and its putative regulators hepatic insulin sensitivity and plasma free fatty acid availability.

Subjects and design: We used stable isotope-labeled tracer methods to evaluate glucose and lipid kinetics in 8 overweight and obese men (age, 38 ± 3 years; body mass index, 33.7 ± 1.7 kg/m(2); means ± SEM) on 2 occasions (randomized crossover design): once, the day after they consumed a balanced diet that provided an amount of energy that matched their energy expenditure, and another time, the day after they consumed a balanced diet that provided 30% excess calories. Eight healthy, lean men (34 ± 1 years; 22.5 ± 0.6 kg/m(2)) were studied under isocaloric conditions only to provide a reference for normal lipid kinetics.

Results: VLDL-TG and VLDL-apolipoprotein B-100 (apoB-100) concentrations and secretion rates were significantly greater (P < .01) in overweight/obese compared with lean men. Hypercaloric, compared with isocaloric, feeding in overweight/obese men increased glucose rate of appearance in plasma (904 ± 21 vs 873 ± 26 μmol/min), the hepatic insulin resistance index (10.9 ± 2.2 vs 8.3 ± 1.8), and VLDL-apoB-100 concentration and secretion rate (1.91 ± 0.24 vs. 1.53 ± 0.13 nmol/min), whereas VLDL-apoB-100 plasma clearance rate, VLDL-TG secretion and plasma clearance rates, and free fatty acid rate of appearance in plasma were not affected by overfeeding.

Conclusion: One day of moderate overfeeding (30% excess energy intake) stimulates hepatic glucose and VLDL-apo B-100 secretion rates but has no effect on hepatic and adipose tissue fatty acid metabolism in overweight/obese men.

Trial registration: ClinicalTrials.gov NCT00830999.

Figure 1.

A–C, VLDL-TG (A) and VLDL–apoB-100 (B) secretion rates into plasma and the molar ratio of VLDL-TG to VLDL–apoB-100 secretion rates (C), an index of the average TG content of newly secreted VLDL particles, in lean and overweight/obese men. Data are means ± SEM. *, Value in the overweight/obese men is significantly different from the corresponding value in lean men, P < .01.

Figure 2.

HIRI on the morning after the isocaloric and hypercaloric study days in overweight/obese men. Data are means ± SEM. *, Value in the hypercaloric trial is significantly different from the corresponding value in the isocaloric trial, P < .05.

Figure 3.

A–C, VLDL-TG (A) and VLDL–apoB-100 (B) secretion rates into plasma and the molar ratio of VLDL-TG to VLDL–apoB-100 secretion rates (C), an index of the average TG content of newly secreted VLDL particles, on the morning after the isocaloric and hypercaloric study days in overweight/obese men. Data are means ± SEM. *, Value in the hypercaloric trial is significantly different from the corresponding value in the isocaloric trial, P < .05.