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Title: Cell-autonomous activation of Hedgehog signaling inhibits brown adipose tissue development

Author
item NOSAVANH, LAGINA - Children'S Nutrition Research Center (CNRC)
item YU, DA-HAI - Baylor College Of Medicine
item JAEHNIG, ERIC - University Of California
item TONG, QIANG - Children'S Nutrition Research Center (CNRC)
item SHEN, LANLAN - Children'S Nutrition Research Center (CNRC)
item CHEN, MIAO-HSUEH - Children'S Nutrition Research Center (CNRC)

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/9/2015
Publication Date: 4/21/2015
Citation: Nosavanh, L., Yu, D., Jaehnig, E.J., Tong, Q., Shen, L., Chen, M. 2015. Cell-autonomous activation of Hedgehog signaling inhibits brown adipose tissue development. Proceedings of the National Academy of Sciences. 112(16):5069-5074.

Interpretive Summary: Brown fat tissue, which uses fat as a fuel source to generate body heat, plays an important role in regulating body weight and insulin sensitivity. The recent rediscovery of brown fat in healthy adult humans suggests that this depot could be used as a potential therapeutic tool for counteracting obesity and type II diabetes. In this study, we showed that mice lose brown fat when Hedgehog signaling is abnormally activated during development. The knowledge from this study helps us better understand how the development of brown fat is controlled in humans.

Technical Abstract: Although recent studies have shown that brown adipose tissue (BAT) arises from progenitor cells that also give rise to skeletal muscle, the developmental signals that control the formation of BAT remain largely unknown. Here, we show that brown preadipocytes possess primary cilia and can respond to Hedgehog (Hh) signaling. Furthermore, cell-autonomous activation of Hh signaling blocks early brown-preadipocyte differentiation, inhibits BAT formation in vivo, and results in replacement of neck BAT with poorly differentiated skeletal muscle. Finally, we show that Hh signaling inhibits BAT formation partially through up-regulation of chicken ovalbumin upstream promoter transcription factor II ("COUP-TFII"). Taken together, our studies uncover a previously unidentified role for Hh as an inhibitor of BAT development.