title: B cell translocation gene 2 (Btg2) is regulated by Stat3 signaling and inhibits adipocyte differentiation.
abstract: Btg2, a member of a family of antiproliferative proteins, is involved in downregulation of the JAK2-Stat3 signaling pathway. Here, we present evidence that the inhibitory effect of Btg2 on adipogenesis is suppressed by the proadipogenic activity of the Stat3 signaling pathway. Btg2 expression fluctuates during adipogenic differentiation of preadipocytes. Btg2 is also expressed at different levels in fat tissues from lean and obese mice. Furthermore, knockdown of Btg2 expression enhanced lipid accumulation and upregulated the expression of adipogenic marker genes. To gain insights into the molecular mechanisms of Btg2 action in adipocytes, adipocytes were treated with previously identified bioactive compounds and the expression of Btg2 was assessed. This effort identified the small molecule WP1066, a known Stat3 inhibitor, as an inducer of Btg2 expression. In line with this observation, siRNA-mediated silencing of Stat3 resulted in upregulated Btg2 expression and decreased lipid accumulation. Furthermore, siRNA-mediated silencing of Btg2 attenuated WP1066-mediated inhibition of adipocyte differentiation. We discuss a model for the role of Btg2 in adipogenesis and propose that Btg2 and Stat3 act in a functional hierarchy.
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Korea.
authors.forename: Suji
authors.initials: S
authors.lastname: Kim
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin, 17104, Korea. jwhong46@khu.ac.kr.
authors.forename: Joung-Woo
authors.initials: JW
authors.lastname: Hong
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Korea. kwpark@skku.edu.
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D017874:Immediate-Early Proteins / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D009765:Obesity / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: C489435:Btg2 protein, mouse; D017874:Immediate-Early Proteins; D011725:Pyridines; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D025521:Tumor Suppressor Proteins; D020032:Tyrphostins; C519885:WP1066
keywords: Adipocyte differentiation; Btg2; Lipid accumulation; Stat3; WP1066