Hepatic lipid metabolic pathways modified by resveratrol in rats fed an obesogenic diet.

Abstract Objective The scientific community is on the look-out for safe biomolecules useful in the prevention of obesity and related aberrations such as fatty liver. This study analyzed the influence of resveratrol on hepatic triacylglycerol metabolism. Methods Male Sprague-Dawley rats were divided into control and resveratrol-treated groups (30 mg/kg of body weight per day) and fed a commercial obesogenic diet for 6 wk. Liver triacylglycerol content and the activity of carnitine palmitoyl transferase-Ia (CPT-Ia), acyl-coenzyme A oxydase (ACO), fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), acetyl-coenzyme A carboxylase (ACC), adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) activation were measured. Mitochondrial protein cytochrome C oxidase subunit 2 (COXII), mitochondrial transcription factor A (TFAM), sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-α (PPAR-α), sirtuin-1 (SIRT1), hepatocyte nuclear factor receptor-4α (HNF-4α), and PGC-1α mRNA levels were also analyzed. Serum insulin was quantified. Results Resveratrol decreased liver fat accumulation, increased CPT-Ia and ACO, and decreased ACC activities. Other lipogenic enzymes, FAS, ME, and G6PDH were not modified. The polyphenol activated AMPK and PGC-1α. The expression of SRBP-1c, PPAR-α, SIRT1, PGC-1α, HNF-4α, TFAM, and COXII was not modified. No changes in serum insulin levels were observed. Conclusion Resveratrol partly prevents the increase in liver fat accumulation induced by high-fat high-sucrose feeding by increasing fatty acid oxidation and decreasing lipogenesis. These effects are mediated by the activation of the AMPK/SIRT1 axis.