Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue.
Chih-Hao WangTadataka TsujiLi-Hong WuCheng-Ying YangTian Lian HuangMari SatoFarnaz ShamsiYu-Hua TsengPublished in: Nature communications (2024)
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.
Keyphrases
- adipose tissue
- insulin resistance
- high fat diet induced
- weight gain
- high fat diet
- endothelial cells
- polycystic ovary syndrome
- body mass index
- birth weight
- cell proliferation
- induced pluripotent stem cells
- pluripotent stem cells
- high glucose
- weight loss
- metabolic syndrome
- poor prognosis
- signaling pathway
- physical activity
- blood pressure
- skeletal muscle
- oxidative stress
- blood glucose
- fatty acid
- pi k akt
- long non coding rna
- glycemic control
- diabetic rats
- risk assessment