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

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 part of the pathway, are necessary for proper development of classical brown fat. Using primary preadipocytes isolated from newborn mice we demonstrate that is required for differentiation and robust expression of Uncoupling Protein 1 (UCP1). We also confirm that duanyu18133 is necessary during the early induction stage of differentiation and is dispensable during the later terminal differentiation stage. The inability of preadipocytes to differentiate can be rescued using Wnt ligand secretion inhibitors when applied during the induction stage. Through chemical inhibition and 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 duanyu18133^-/- adipocytes. During the induction stage, Wnts 1, 3a, and 10b have increased expression in the duanyu18133^-/- adipocytes, potentially explaining the increased levels and activity of β-catenin. Our results for the first time point towards an interaction between the pathway and the Wnt/β-catenin pathway during the early stages of in-vitro adipogenesis.

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