[Effects of calorie restriction on SIRT1 expression in liver of nonalcoholic fatty liver disease: experiment with rats].
OBJECTIVE
To investigate the molecular mechanisms of calorie restriction (CR) in treatment of nonalcoholic fatty liver disease (NAFLD).


METHODS
25 male Wistar rats were randomly divided into 2 groups: normal control group (NC, n = 7) fed with regular diet and high fat diet-NAFLD model group (HFM, n = 18) fed with high-fat diet. Two months later, the rats in Group HFM were further divided into 2 subgroups: continuous high-fat feeding group (HF, n = 9) and normal diet feeding with 60% calorie restriction group (CR, n = 9). The rats were sacrificed after 1 month calorie restriction. By the end of experiment, body weight (BW), visceral fat mass (VF), fasting plasma glucose (FPG), fasting serum insulin (FINS), blood lipids (BL), including total cholesterol (TC) and triglyceride (TG), and hepatoultrastructure changes were examined to evaluate the effect of different feeding protocols on the experimental animals. The mRNA expression of the longevity gene SIRT1 in the liver was detected by RT-PCR. Western blot analysis was performed to determine the expression of SIRT1 protein in each group.


RESULTS
Electron microscopy showed that the rats in group HF displayed obviously abnormal hepatoultrastructure, and the ultramicropathology changes of liver cell were improved obviously in Group CR. The VF, FINS, FPG, TC, and TG of the Group HF were 15.1 g +/- 4.1 g, 29.22 mU/L +/- 7.28 mU/L, 6.2 mmol/L +/- 1.46 mmol/L, 2.61 mmol/L +/- 0.29 mmol/L, and 1.35 mmol/L +/- 0.21 mmol/L respectively, all significantly higher than those in Group NC (9.0 g +/- 0.4 g, 13.09 mU/L +/- 1.18 mU/L, 4.4 mmol/L +/- 0.57 mmol/L, 1.41 mmol/L +/- 0.28 mmol/L, and 0.67 mmol/L +/- 0.10 mmol/L respectively, all P < 0.01). The mRNA expression of SIRT1 in the liver of Group HF was significantly lower than that of Group NC (P < 0.05), and the mRNA expression of SIRT1 in the liver of Group CR was significantly higher than those of Group HF and Group NC (both P < 0.01). The protein expression of SIRT1 of Group HF was significantly lower than that of Group NC (P < 0.01), and that of Group CR was significantly higher than that of Group HF, however, still significantly lower than that of Group NC (both P < 0.01). The BW and VF, FINS, FPG, TC, and TG of Group CR were all significantly lower than those of Group HF (all P < 0.01).


CONCLUSIONS
CR can reverse NAFLD significantly. The increased expression of SIRT1 in liver induced by CR may be an important molecular mechanism involved in the improvement of NAFLD by CR.
Chen
Lu-lu
LL
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430022, China.
Deng
Xiang-qun
XQ
Li
Ning-xu
NX
D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000178:diet therapy*; D015870:Gene Expression; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1; D037761:Sirtuins / Q000096:biosynthesis / Q000235:genetics*