Effects of a low-fat, high-carbohydrate diet on VLDL-triglyceride assembly, production, and clearance

Abstract

Low-fat, high-carbohydrate (LF/HC) diets commonly elevate plasma triglyceride (TG) concentrations, but the kinetic mechanisms responsible for this effect remain uncertain. Subjects with low TG (normolipidemic [NL]) and those with moderately elevated TG (hypertriglyceridemic [HTG]) were studied on both a control and an LF/HC diet. We measured VLDL particle and TG transport rates, plasma nonesterified fatty acid (NEFA) flux, and sources of fatty acids used for the assembly of VLDL-TG. The LF/HC diet resulted in a 60% elevation in TG, a 37% reduction in VLDL-TG clearance, and an 18% reduction in whole-body fat oxidation, but no significant change in VLDL-apo B or VLDL-TG secretion rates. Significant elevations in fasting apo B-48 concentrations were observed on the LF/HC in HTG subjects. In both groups, fasting de novo lipogenesis was low regardless of diet. The NEFA pool contributed the great majority of fatty acids to VLDL-TG in NL subjects on both diets, whereas in HTG subjects, the contribution of NEFA was somewhat lower overall and was reduced further in individuals on the LF/HC diet. Between 13% and 29% of VLDL-TG fatty acids remained unaccounted for by the sum of de novo lipogenesis and plasma NEFA input in HTG subjects. We conclude that (a) whole-food LF/HC diets reduce VLDL-TG clearance and do not increase VLDL-TG secretion or de novo lipogenesis; (b) sources of fatty acids for assembly of VLDL-TG differ between HTG and NL subjects and are further affected by diet composition; (c) the presence of chylomicron remnants in the fasting state on LF/HC diets may contribute to elevated TG levels by competing for VLDL-TG lipolysis and by providing a source of fatty acids for hepatic VLDL-TG synthesis; and (d) the assembly, production, and clearance of elevated plasma VLDL-TG in response to LF/HC diets therefore differ from those for elevated TG on higher-fat diets.

Figure 1

Stable isotope infusion protocol. Subjects were admitted to the GCRC for a 24-hour isotope infusion study; protocol and calculations are described in the text.

Figure 2

Percentage of VLDL-TG palmitate derived from the plasma NEFA pool. Data are from 2 representative subjects on the control diet: an NL subject (top) and an HTG subject (bottom). The infusion of [1,2,3,4-¹³C₄]palmitate (from 0400 to 1600 hours) reached steady state within the plasma NFA pool 1 hour after the start of the infusion.

Figure 3

Apolipoprotein (apo) concentrations in the TG-rich lipoprotein (TRL) fraction in HTG subjects. Values are mean ± SEM. *P < 0.05, comparison between dietary treatments.

Figure 4

Sources of VLDL-TG palmitic acid. Values are mean ± SEM. The numbers on the bars represent the percentages of VLDL-TG palmitate derived from the NEFA pool alone (darker portion of the bar).