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Updated: Jun 15, 2025

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
Published on: March 28, 2013
Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue
Chih-Hao Wang1,2,3, Tadataka Tsuji4, Li-Hong Wu5
1Graduate Institute of Cell Biology, China Medical University, Taichung City, Taiwan. chih-hao.wang@cmu.edu.tw.
Abstract:
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.
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