STAT3 suppresses Wnt/β-catenin signaling during the induction phase of primary Myf5+brown adipogenesis

被引：11

作者：

Cantwell, Marc T. ^{[1
]}

Farrar, Jared S. ^{[1
]}

Lownik, Joseph C. ^{[1
]}

Meier, Jeremy A. ^{[1
]}

Hyun, Moonjung ^{[2
,3
]}

Raje, Vidisha ^{[4
]}

Waters, Michael R. ^{[2
,3
]}

Celi, Francesco S. ^{[5
]}

Conrad, Daniel H. ^{[6
]}

Harris, Thurl E. ^{[4
]}

Larner, Andrew C. ^{[2
,3
]}

机构：

[1] Virginia Commonwealth Univ, Sch Med, Ctr Clin & Translat Res, Richmond, VA 23298 USA

[2] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA

[3] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA

[4] Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22908 USA

[5] Virginia Commonwealth Univ, Sch Med, Dept Internal Med, Div Endocrinol Diabet & Metab, Richmond, VA 23298 USA

[6] Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, Richmond, VA 23298 USA

来源：

CYTOKINE | 2018年 / 111卷

关键词：

Adipogenesis; STAT3; Wnt; beta-Catenin; BAT; UCP1; BROWN ADIPOSE-TISSUE; DIFFERENTIATION; INHIBITION; PATHWAY; TRANSCRIPTION-3; TRANSDUCER; ACTIVATION; PROMOTES; BINDING; OBESITY;

D O I：

10.1016/j.cyto.2018.05.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Thermogenic fat is a promising target for new therapies in diabetes and obesity. Understanding how thermogenic fat develops is important to develop rational strategies to treat obesity. Previously, we have shown that Tyk2 and STAT3, part of the JAK-STAT pathway, are necessary for proper development of classical brown fat. Using primary preadipocytes isolated from newborn mice we demonstrate that STAT3 is required for differentiation and robust expression of Uncoupling Protein 1 (UCP1). We also confirm that STAT3 is necessary during the early induction stage of differentiation and is dispensable during the later terminal differentiation stage. The inability of STAT3(-/-) preadipocytes to differentiate can be rescued using Wnt ligand secretion inhibitors when applied during the induction stage. Through chemical inhibition and RNAi, we show that it is the canonical beta-catenin pathway that is responsible for the block in differentiation; inhibition or knockdown of beta-catenin can fully rescue adipogenesis and UCP1 expression in the STAT3(-/-) adipocytes. During the induction stage, Wnts 1, 3a, and 10b have increased expression in the STAT3(-/-) adipocytes, potentially explaining the increased levels and activity of beta-catenin. Our results for the first time point towards an interaction between the JAK/STAT pathway and the Wnt/beta-catenin pathway during the early stages of in-vitro adipogenesis.

引用

页码：434 / 444

页数：11