High-Dose Resveratrol Treatment for 2 Weeks Inhibits Intestinal and Hepatic Lipoprotein Production in Overweight/Obese Men

Abstract

Objective-Overproduction of hepatic apolipoprotein B (apoB)-100 containing very low-density lipoprotein particles and intestinal apoB-48 containing chylomicrons contributes to hypertriglyceridemia seen in conditions such as obesity and insulin resistance. Some, but not all, preclinical and clinical studies have demonstrated that the polyphenol resveratrol ameliorates insulin resistance and hypertriglyceridemia. Here, we assessed intestinal and hepatic lipoprotein turnover, in humans, after 2 weeks of treatment with resveratrol (1000 mg daily for week 1 followed by 2000 mg daily for week 2) or placebo. Approach and Results-Eight overweight or obese individuals with mild hypertriglyceridemia were studied on 2 occasions, 4 to 6 weeks apart, after treatment with resveratrol or placebo in a randomized, double-blinded, crossover study. Steadystate lipoprotein kinetics was assessed in a constant fed state with a primed, constant infusion of deuterated leucine.Resveratrol treatment did not significantly affect insulin sensitivity (homeostasis model of assessment of insulin resistance), fasting or fed plasma triglyceride concentration. Resveratrol reduced apoB-48 production rate by 22% (P=0.007) with no significant effect on fractional catabolic rate. Resveratrol reduced apoB-100 production rate by 27% (P=0.02) and fractional catabolic rate by 26% (P=0.04). Conclusions-These results indicate that 2 weeks of high-dose resveratrol reduces intestinal and hepatic lipoprotein particle production. Long-term studies are needed to evaluate the potential clinical benefits of resveratrol in patients with hypertriglyceridemia, who have increased concentrations of triglyceride-rich lipoprotein apoB-100 and apoB-48. Clinical Trial Registration-URL: www.clinicaltrials.gov. Unique identifier: NCT01451918. AMPK also has indirect effects such as activation of SIRT1. SIRT1, thought to mediate many of the beneficial effects of caloric restriction, deacetylates multiple targets including peroxisome proliferator-activated receptor coactivator-1α, FoxO1, AMPK itself, and nuclear factor κB, thereby influencing lipid and glucose metabolism as well as inflammation 19,20 No studies to date, either in rodents or humans, have assessed the effects of resveratrol on lipoprotein production and clearance. Therefore, we sought to assess the effects of short-term administration of high-dose resveratrol on intestinal and hepatic lipoprotein turnover as well as insulin sensitivity in nondiabetic, overweight, and obese men with mild hypertriglyceridemia. Although in most human studies, resveratrol was administered for ≥4 weeks, many of these studies used low doses (≤150 mg/d) 14,15 with positive metabolic effects. Dose-dependent increases in plasma concentrations of resveratrol (at doses between 0.5 and 5 g) have been reported previously with higher elimination half-lives of doses between 1 and 2.5 g (>9 hours) compared with the lower dose of 0.5 g (o>4 hours). 21 We hypothesized that higher doses of resveratrol could elicit beneficial effects on TRL metab...

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

“…In contrast to these aforementioned studies, resveratrol had no effect on lipid profile in several other studies [78,79,82,138,139]. In addition, a meta-analysis of 7 clinical trials concluded that resveratrol lacks a significant effect on plasma lipid concentrations [140].…”

Resveratrol and obesity: Can resveratrol relieve metabolic disturbances?

“…Increasing the amount of physical 53 activity or decreasing energy intake are proven effective therapeutic 54 strategies to positively influence health outcomes related to obesity. 55 Correspondingly, restricting calorie intake for six months leads to an im- 56 provement in insulin sensitivity [6], which in turn is accompanied by an 57 increase in muscle mitochondrial biogenesis [7]. However, people in 58 general have difficulties following strict exercise training or dieting 59 regimes.…”

Resveratrol: Is It Really Good for Liver Health?

“…In another randomized, doubleblind, crossover study conducted on 11 healthy males with obesity with placebo and 150 mg/day RES for 30 days RES supplementation induced metabolic changes in individuals with obesity, mimicking the effects of calorie restriction (57). Similarly, a 2-week, high-dose RES treatment (1 g daily for 1 week followed by 2 g daily for 2 weeks) significantly reduced intestinal and hepatic lipoprotein particle production (58). In contrast to these reports, RES supplementation had no beneficial metabolic effects on nonobese, postmenopausal females with normal glucose tolerance when given at a dose of 75 mg/day for 12 weeks (59).…”