Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue.

Autor: Wang CH; Graduate Institute of Cell Biology, China Medical University, Taichung City, Taiwan. chih-hao.wang@cmu.edu.tw.; Graduate Institute of Biomedical Sciences, China Medical University, Taichung City, Taiwan. chih-hao.wang@cmu.edu.tw.; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. chih-hao.wang@cmu.edu.tw., Tsuji T; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA., Wu LH; Graduate Institute of Cell Biology, China Medical University, Taichung City, Taiwan., Yang CY; Graduate Institute of Biomedical Sciences, China Medical University, Taichung City, Taiwan., Huang TL; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA., Sato M; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA., Shamsi F; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.; Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY, USA., Tseng YH; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. yu-hua.tseng@joslin.harvard.edu.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. yu-hua.tseng@joslin.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 22; Vol. 15 (1), pp. 7215. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1038/s41467-024-51579-0
Abstrakt: Thermogenic adipose tissue, consisting of brown and beige fat, regulates nutrient utilization and energy metabolism. Human brown fat is relatively scarce and decreases with obesity and aging. Hence, inducing thermogenic differentiation of white fat offers an attractive way to enhance whole-body metabolic capacity. Here, we show the role of endothelin 3 (EDN3) and endothelin receptor type B (EDNRB) in promoting the browning of white adipose tissue (WAT). EDNRB overexpression stimulates thermogenic differentiation of human white preadipocytes through cAMP-EPAC1-ERK activation. In mice, cold induces the expression of EDN3 and EDNRB in WAT. Deletion of EDNRB in adipose progenitor cells impairs cold-induced beige adipocyte formation in WAT, leading to excessive weight gain, glucose intolerance, and insulin resistance upon high-fat feeding. Injection of EDN3 into WAT promotes browning and improved whole-body glucose metabolism. The findings shed light on the mechanism of WAT browning and offer potential therapeutics for obesity and metabolic disorders.
(© 2024. The Author(s).)
Databáze: MEDLINE
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