Weight loss due to energy restriction suppresses cholesterol biosynthesis in overweight, mildly hypercholesterolemic men

Mechanisms explaining the decrease in circulatory cholesterol levels after weight loss remain ill defined. The objective was to examine effects of wei ght loss as achieved through energy restriction upon human in vivo choleste rol biosynthesis. Six subjects (64-77 y, body mass index, 30.3 +/- 3.8 kg/m (2)) were recruited into a two-phase prospective clinical trial. In the fir st phase, subjects complied with American Heart Association (AHA) Step I di ets for 3 mo with no change in their usual energy intake. After this weight -stable phase, subjects consumed an AHA Step I diet with a targeted reducti on in energy intake of similar to 1000 kJ/d for 6 mo to achieve negative en ergy balance leading to weight loss. The incorporation rate of deuterium fr om body water into erythrocyte membrane free cholesterol over 24 h was util ized as an index of cholesterogenesis at the end of both phases. Subjects' mean weights decreased (P < 0.05) from 89.3 +/- 12.5 kg to 83.2 +/- 11.5 kg (6.8 +/- 2.6% of initial body weight) across phases. Circulating concentra tions of total and LDL-cholesterol, and triglycerides also decreased (P < 0 .05) across phases. HDL-cholesterol concentrations were unchanged (P > 0.05 ), Cholesterol fractional synthetic rate (FSR) after phase 2 (3.04 +/- 1.90 %/d) was lower (P < 0.05) than that after phase 1 (8.42 +/- 3.90%/d). Absol ute synthesis rate (ASR) after phase 2 [0.59 +/- 0.38 g/(kg . d)] also was lower (P < 0.05) than that after phase 1 [1.66 +/- 0.84 g/(kg . d)]. These data suggest that, in obese men, energy restriction resulting in even modes t weight loss suppresses endogenous cholesterol synthesis, which contribute s to a decline in circulating lipid concentrations.