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Updated: Jul 17, 2026

Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice
Published on: February 3, 2023
Deleting Bmp4 in brown fat unlocks an arachidonic acid-AMPK axis to boost energy expenditure
Yan-Jue Song1, Ting Meng1, Zhen-Yu Xu1
1Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai, China.
Abstract:
Fasting enhances lipolysis in white adipose tissue (WAT), releasing fatty acids (FAs) which are subsequently metabolized through β-oxidation in the liver and brown adipose tissue (BAT). Although BAT is a key site for FA utilization, the specific FAs taken up and oxidized during fasting-as well as their systemic metabolic effects-remain poorly defined. Time-course analysis revealed that fasting reprograms BAT to promote the esterification and storage of circulating FAs rather than their immediate oxidation. This lipid pool was selectively enriched in long-chain polyunsaturated fatty acids (LCPUFAs), particularly arachidonic acid (AA). Genetic (BAT-specific knockout of bone morphogenetic protein 4, Bmp4) or pharmacological (Inhibition of diacylglycerol acyltransferase, DGAT) disruption of this FA esterification process potently enhanced mitochondrial function and systemic energy expenditure. Mechanistically, AA activated AMP-activated protein kinase (AMPK), thereby enhancing energy expenditure through increased mitochondrial biogenesis. Our work reveals a fasting-inducible, AA-centric signaling pathway that senses lipid storage status. Through activation of AMPK, it couples suppressed FA esterification to enhanced oxidation, positioning BMP4 as a critical regulator of this metabolic switch.
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