Resveratrol up-regulates hepatic uncoupling protein 2 and prevents development of nonalcoholic fatty liver disease in rats fed a high-fat diet.
Obesity is associated with a markedly increased risk of nonalcoholic fatty liver disease. The anti-inflammatory polyphenol resveratrol possess promising properties in preventing this metabolic condition by dampening the pathological inflammatory reaction in the hepatic tissue. However, in the current study, we hypothesize that the beneficial effect of resveratrol is not solely attributable to its anti-inflammatory potential. Eight-week-old male Wistar rats were randomly distributed into 3 groups of 12 animals each: control diet (C), high-fat diet (HF), and HF supplemented with 100 mg resveratrol daily (HFR). After 8 weeks of dietary treatment, the rats were euthanized and relevant tissues were prepared for subsequent analysis. Resveratrol prevented the high fat-induced steatosis assessed by semiquantitative grading, which furthermore corresponded with a complete normalization of the hepatic triglyceride content (P < .001), despite no change in total body fat. In HFR, the hepatic uncoupling protein 2 expression was significantly increased by 76% and 298% as compared with HF and C, respectively. Moreover, the hepatic mitochondria content in HFR was significantly higher as compared with both C and HF (P < .001 and P = .004, respectively). We found no signs of hepatic inflammation, hereby demonstrating that resveratrol protects against fatty liver disease independently of its proposed anti-inflammatory potential. Our data might indicate that an increased number of mitochondria and, particularly, an increase in hepatic uncoupling protein 2 expression are involved in normalizing the hepatic fat content due to resveratrol supplementation in rodents fed a high-fat diet.
Department of Endocrinology and Internal Medicine MEA, Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Århus C, Denmark. mmp@ki.au.dk
Morten Møller
MM
Poulsen
Jens Ø
JØ
Larsen
Stephen
S
Hamilton-Dutoit
Berthil F
BF
Clasen
Niels
N
Jessen
Søren K
SK
Paulsen
Thomas N
TN
Kjær
Bjørn
B
Richelsen
Steen B
SB
Pedersen
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D059305:Diet, High-Fat; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy / Q000517:prevention & control*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D014280:Triglycerides / Q000378:metabolism; D000071246:Uncoupling Protein 2; D015854:Up-Regulation
D015415:Biomarkers; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D013267:Stilbenes; D014280:Triglycerides; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D000077185:Resveratrol