title: Cyclin Y Is Involved in the Regulation of Adipogenesis and Lipid Production.
abstract: A new member of the cyclin family cyclin Y (CCNY) is involved in the regulation of various physiological processes. In this study, the role of CCNY in energy metabolism was characterized. We found that compared with wild-type (WT) mice, Ccny knockout (KO) mice had both lower body weight and lower fat content. The Ccny KO mice also had a higher metabolic rate, resisted the stress of a high-fat diet, and were sensitive to calorie restriction. The expression levels of UCP1 and PGC1α were significantly higher in the brown adipose tissue (BAT) of the Ccny KO mice than that of the WT littermate controls, whereas there was no significant difference in BAT weight between the WT and the Ccny KO mice. In addition, the down-regulation of Ccny resulted in suppression of white adipocyte differentiation both in vivo and in vitro, while the expression of Ccny was up-regulated by C/EBPα. Furthermore, both hepatocytes and HepG2 cells that were depleted of Ccny were insensitive to insulin stimulation, consistent with the significant inhibition of insulin sensitivity in the liver of the Ccny KO mice, but no significant changes in WAT and muscle, indicating that CCNY is involved in regulating the hepatic insulin signaling pathway. The hepatic insulin resistance generated by Ccny depletion resulted in down-regulation of the sterol-regulatory element-binding protein (SREBP1) and fatty acid synthase (FASN). Together, these results provide a new link between CCNY and lipid metabolism in mice, and suggest that inhibition of CCNY may offer a therapeutic approach to obesity and diabetes.
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: An
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Zhuzhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China; Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Wu
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D031204:Caloric Restriction; D002454:Cell Differentiation / Q000187:drug effects; D016213:Cyclins / Q000172:deficiency / Q000378:metabolism*; D059305:Diet, High-Fat; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008055:Lipids / Q000096:biosynthesis*; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects; D022722:Thermogenesis / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D016213:Cyclins; D007328:Insulin; D008055:Lipids; C000606718:cyclin Y, mouse