ABSTRACT
The sirtuin proteins are nicotinamide adenine dinucleotide dependent deacetylases and adenosine diphosphate (ADP)-ribosyl transferases associated with metabolic balance and lifespan extension. Sirtuin 1 (SIRT1) and sirtuin 4 (SIRT4) have been reported to regulate insulin secretion, but their association with the development of insulin resistance and nonalcoholic fatty liver disease remain undefined. The aim of this study was to determine the expression of SIRT1 and SIRT4 in the liver and pancreas of rats fed with different diets and analyze the association of these proteins with insulin resistance and nonalcoholic fatty liver disease. Male Sprague-Dawley rats were randomly divided into the following 4 diet treatment groups: normal control (NC), calorie restriction (CR), high-fat (HFa), and high-fructose (HFr), and these groups were maintained for 12 weeks. Blood biochemical analysis and histopathology indicated that HFa and HFr groups were insulin resistant and developed nonalcoholic fatty livers. SIRT1 was present in the nucleus and cytoplasm of the pancreatic beta-cells, while SIRT4 was located in the cytoplasm. Treatment with the CR diet increased the expression of SIRT1 in both the pancreas and liver, while treatment with the HFa and HFr diets caused a decrease. SIRT4 was upregulated in the liver of rats treated with the HFa diet, but did not change with the CR diet treatment. These data suggest that SIRT1 and SIRT4 were both involved in the development of insulin resistance and nonalcoholic fatty liver disease.
Subject(s)
Caloric Restriction , Insulin Resistance/physiology , Sirtuin 1/metabolism , Sirtuins/metabolism , Animals , Blood Glucose/metabolism , Blood Glucose/physiology , Body Weight/physiology , Cholesterol/blood , Fasting/blood , Fatty Liver/etiology , Fatty Liver/metabolism , Insulin/metabolism , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/physiology , Male , Non-alcoholic Fatty Liver Disease , Rats , Rats, Sprague-Dawley , Triglycerides/bloodABSTRACT
Recent studies in mice have shown that resveratrol can protect the liver from fat accumulation induced by high fat diet. However, the exact mechanism is largely unknown. To explore the possible mechanism, we investigated the anti-lipogenic effect of resveratrol in vitro model. Oil Red O staining revealed that resveratrol could significantly ameliorate the excessive triglyceride accumulation in HepG2 cells induced by palmitate. The results of RT-PCR and Western blotting showed that resveratrol upregulated the expression of Sirt1 and forkhead box O1 (FOXO1), whereas downregulated the expression of sterol regulatory element binding protein1 (SREBP1). Moreover, resveratrol was shown to inhibit the activity of SREBP1, as evaluated by immunofluorescence assay. Our results suggest that resveratrol may attenuate fat deposition by inhibiting SREBP1 expression via Sirt1-FOXO1 pathway and thus may have application for the treatment of NAFLD.
