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Abstract This study aimed at exploring the inhibition of silence information regulator1 (Sirt1) on fat deposition of mice and the influence of mammalian target of rapamycin (mTOR) pathway. Mice(Mus mussulus) were treated with the activator of Sirt1 resveratrol (100 mg·kg-1·d-1) and the antagonists nicotinamide (100 mg·kg-1·d-1) by gavage daily for 15 days. The body weight, subcutaneous fat tissue, periepdidymal fat pads and perirenal fat pads were weighed, while the concentrations of triglycerides(TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were measured by Kits. The mRNA expression of transcriptional regulation factors peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1) as well as adipose decompose related gene adipose triglyceride lipase (ATGL), homrnoe-snestive lipaes (HSL), perilipin and fat synthesis gene fatty acid synthetase (FAS) mRNA were measured by Real-time PCR. Simultaneously, the levels of the key factors of mTOR pathway mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4EBP1) and P70 ribosomal protein S6 kinases 1 (S6K1) mRNA were also measured by Real-time PCR. Compared with the control, resveratrol could decreased the increase of body mass and the body fat content(P<0.01), obviously decreased the concentrations of TG, TC and LDL-C in blood serum (P<0.01), and visibly increased the concentrations of HDL-C(P<0.01). The expression levels of the key fatcors of mTOR pathway: mTOR, 4EBP1 and S6K1 mRNA, were down-regulated(P<0.01), the major transcriptional factors PPARγ, SREBP1 and fat synthesis gene FAS mRNA were also distinctly reduced(P<0.01), while the mRNA expression of adipose decompose related genes ATGL, HSL and Perilipin mRNA were up-regulated significantly(P<0.01). Body weight, periepdidymal fat pads and subcutaneous fat tissue increased a little(P>0.05) in nicotinamide-treatment mice, while perirenal fat pads increased(P<0.05), the levels of HDL-C up-regulated(P<0.05) as well as LDL-C reduced significantly(P<0.01) in nicotinamide-treatment mice. The expression levels of the key factors of mTOR pathway mTOR and 4EBP1 mRNA were obviously down-regulated(P<0.01), and the major transcriptional factors PPARγ and SREBP1 mRNA increased(P<0.05), as well as adipose decompose related gene ATGL mRNA decreased(P<0.05), but the expression of HSL and Perilipin were not significant(P>0.05), and the expression levels of fat synthesis gene FAS were also not significant(P>0.05).We demonstrated that activate Sirt1 can reduce fat synthesis, increase fat breakdown and reduce body fat deposition, and mTOR pathway involves in this process.
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Received: 08 September 2011
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