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

Marc T. Cantwell, Jared S. Farrar, Joseph C. Lownik, Jeremy A. Meier, Moonjung Hyun, Vidisha Raje, Michael R. Waters, Francesco S. Celi, Daniel H. Conrad, Thurl E. Harris, Andrew C. Larner

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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 β-catenin pathway that is responsible for the block in differentiation; inhibition or knockdown of β-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 β-catenin. Our results for the first time point towards an interaction between the JAK/STAT pathway and the Wnt/β-catenin pathway during the early stages of in-vitro adipogenesis.

Original languageEnglish
Pages (from-to)434-444
Number of pages11
JournalCytokine
Volume111
DOIs
StatePublished - Nov 2018

Keywords

  • Adipogenesis
  • BAT
  • STAT3
  • UCP1
  • Wnt
  • β-Catenin

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