Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity.
In this study, we aimed to investigate the protective effects and underlying mechanism of Lycium barbarum polysaccharide (LBP) on high-fat-induced nonalcoholic fatty liver disease (NAFLD). Recently, sirtuin 1 (SIRT1) has been shown to play an important role in the regulation of hepatocellular lipid metabolism. Here, we demonstrated that LBP up-regulates SIRT1 deacetylase activity and protein expression by enhancing the NAD+/NADH ratio. Subsequently, LBP promoted LKB1 deacetylation and AMPK phosphorylation via SIRT1-dependent signalling. We also found that LBP increases acetyl-CoA carboxylase (ACC) phosphorylation and adipose triglyceride lipase (ATGL) protein expression and decreases fatty acid synthase (FAS) by activating the SIRT1/LKB1/AMPK pathway in vitro and in vivo. However, SIRT1 small interfering RNA (siRNA)-mediated knockdown reversed the LBP-mediated effects on ACC, FAS and ATGL. Moreover, LBP elevated carnitine palmitoyltransferase-1 alpha (CPT-1α) expression by suppressing malonyl-CoA accumulation. Taken together, our data indicate that LBP plays a vital role in the regulation of hepatic lipid metabolism and that pharmacological activation of SIRT1 by LBP may be a strategy for the prevention of NAFLD.
Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.|Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, China.
Li
L
Jia
Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.|Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, China.
Wang
W
Li
Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.|Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, China.
Jianning
J
Li
Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.|Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, China.
Yan
Y
Li
Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, China.
Hui
H
Song
Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.|Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, China.
Yansong
Y
Luan
Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.|Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, China.
Hui
H
Qi
Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.|Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, China.
Lirong
L
Ma
Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.|Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, China.
Xiaohong
X
Lu
Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.|Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, China.
Yi
Y
Yang
D055372:AMP-Activated Protein Kinases; D000107:Acetylation; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009243:NAD / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
D004365:Drugs, Chinese Herbal; C500223:lycium barbarum polysaccharide; D009243:NAD; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1