Objective: SIRT1 is an NAD⁺‐dependent deacetylase and its enzymatic activity may be regulated by cellular energy. SIRT1 overexpression reduces the level of oxygen consumption, which is correlative with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of SIRT1 on the development of NAFLD, we investigated the expression of SIRT1 in NAFLD induced by high‐fat diet in rats and the effects of calorie restriction.

Methods: Thirty‐one male Wistar rats were divided at random into four groups. The rats in the normal control group NC (n=7) and in the NAFLD model group HF (n=9) were fed ad libitum with normal chow and high‐fat diet, respectively, for 3 months, the rats in the calorie restriction (CR) group HCR (n=9) were fed with a high‐fat diet for 2 months and then 60% CR with normal chow for 1 month, and the rats in group CRH (n=6) were firstly fed with 60% CR with normal chow for 1 month and then fed a high‐fat diet for 2 months. At the end of the experiment, some parameters and expressions of SIRT1 were detected.

Results: The rats in group HF displayed NAFLD. Compared with group NC, the expression of SIRT1 protein was significantly decreased (P<0.01). However, the lower body weight and visceral fat mass of rats in group HCR were showed. Compared with group HF, CR increased the expression of SIRT1 in liver significantly (P<0.01). Consequently, the ultramicropathology changes of NAFLD prominently improved in this group. Meanwhile, the rats in group CRH displayed higher expression of SIRT1 protein and very gentle pathology changes of NAFLD.

Conclusion: The expression of SIRT1 is reduced significantly in NAFLD induced by high‐fat diet in rats. CR increase‐SIRT1 protein expression may be an important mechanism by which CR improves NAFLD.