title: Retinol-Binding Protein 4 Induces Hepatic Mitochondrial Dysfunction and Promotes Hepatic Steatosis.
abstract: Elevated serum retinol-binding protein 4 (RBP4) has been implicated in insulin resistant and nonalcoholic fatty liver disease (NAFLD) subjects; however, the molecular mechanism of RBP4 in NAFLD remains obscure.
  
  
  
  Hepatic RBP4 mRNA level and its association with lipid accumulation were examined in NAFLD patients and mouse model. Furthermore, human RBP4 overexpressing (RBP4-Tg) mice were metabolically phenotyped after either a regular chow or high-fat diet.
  
  
  
  RBP4 mRNA was aberrantly elevated in NAFLD models and positively associated with increased hepatic triglyceride accumulation. Compared with their wild-type littermates, RBP4-Tg mice fed regular chow had increased hepatic lipid accumulation associated with cellular ballooning and inflammatory changes, which was exacerbated when challenged with high-fat diet. The acceleration of NAFLD in RBP4-Tg mice was mainly attributed to reduced mitochondrial content and impaired mitochondrial fatty acid β-oxidation. RBP4 overexpression promoted the acetylation of long-chain acyl-coenzyme A dehydrogenase through inhibiting the expression and activity of NAD-dependent deacetylase sirtuin-3 and significantly hampered the binding of long-chain acyl-coenzyme A dehydrogenase and NAD-dependent deacetylase sirtuin-3. Moreover, RBP4-induced mitochondrial dysfunction preceded the deterioration of lipid metabolism.
  
  
  
  These results have unraveled a novel role of RBP4 in hepatic mitochondrial dysfunction and steatosis and suggest that RBP4 might be a potential target for the early prevention of NAFLD.
authors: Guangdong Provincial Key Laboratory of Food, Nutrition and Health (Y.L., D.M., M.X.) and Department of Nutrition (Y.L., D.M., H.C., D.L., J.S., Y.Z., M.X.), School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, Guangdong Province, China.
authors: Yan
authors: Y
authors: Liu
authors: Guangdong Provincial Key Laboratory of Food, Nutrition and Health (Y.L., D.M., M.X.) and Department of Nutrition (Y.L., D.M., H.C., D.L., J.S., Y.Z., M.X.), School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, Guangdong Province, China.
authors: Di
authors: D
authors: Mu
authors: Guangdong Provincial Key Laboratory of Food, Nutrition and Health (Y.L., D.M., M.X.) and Department of Nutrition (Y.L., D.M., H.C., D.L., J.S., Y.Z., M.X.), School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, Guangdong Province, China.
authors: Hongen
authors: H
authors: Chen
authors: Guangdong Provincial Key Laboratory of Food, Nutrition and Health (Y.L., D.M., M.X.) and Department of Nutrition (Y.L., D.M., H.C., D.L., J.S., Y.Z., M.X.), School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, Guangdong Province, China.
authors: Di
authors: D
authors: Li
authors: Guangdong Provincial Key Laboratory of Food, Nutrition and Health (Y.L., D.M., M.X.) and Department of Nutrition (Y.L., D.M., H.C., D.L., J.S., Y.Z., M.X.), School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, Guangdong Province, China.
authors: Jiayi
authors: J
authors: Song
authors: Guangdong Provincial Key Laboratory of Food, Nutrition and Health (Y.L., D.M., M.X.) and Department of Nutrition (Y.L., D.M., H.C., D.L., J.S., Y.Z., M.X.), School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, Guangdong Province, China.
authors: Yuan
authors: Y
authors: Zhong
authors: Guangdong Provincial Key Laboratory of Food, Nutrition and Health (Y.L., D.M., M.X.) and Department of Nutrition (Y.L., D.M., H.C., D.L., J.S., Y.Z., M.X.), School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, Guangdong Province, China.
authors: Min
authors: M
authors: Xia
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D028361:Mitochondrial Diseases / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*
chemical_list: C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma