title: Enhanced expression of Survivin has distinct roles in adipocyte homeostasis.
abstract: Although precisely controlled lipolysis is crucial for maintaining physiological levels of circulating free fatty acids in response to energetic stress, the underlying mechanisms by which this process is governed remain poorly understood. Survivin is a gene that has been found to be highly expressed in the most common human tumors, and it is considered to be associated with tumorigenesis. Survivin expression in normal tissue is developmentally downregulated and is undetectable in most terminally differentiated adult tissues. Here, we report that Survivin expression in mature adipocytes from murine white adipose tissue can be highly induced under high-fat diet feeding conditions. During the adipocyte differentiation of 3T3-L1 preadipocytes and mesenchymal C3H10T1/2 cells, Survivin expression is gradually decreased and almost undetectable in fully differentiated adipocytes. However, it can be expressed again upon insulin exposure, through the PI3K/mTOR signaling pathway. Nevertheless, Survivin overexpression is sensitive to nutritional deprivation, and expression markedly decreases in response to starvation with Hank's buffered salt solution challenge. The ectopic expression of Survivin downregulates expression of Adrb3 and then decreases the production of cAMP, while Fsp27 protein levels are upregulated as a result of reduced protein degradation. This in turn inhibits isoproterenol-stimulated adipocyte lipolysis. Survivin also attenuates DNA damage related to PARP activation and inhibits TNFα-induced lipolysis, suggesting that Survivin may facilitate adipocyte maintenance in response to inflammatory stimuli. Further studies will be undertaken to determine whether Survivin is critical for lipid storage to maintain metabolic homeostasis in vivo.
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Ju
authors.affiliation: Department of Endocrine and Metabolic Diseases, Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Endcrinology, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Endocrine and Metabolic Diseases, Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Qichen
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D000077022:Survivin; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases