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- Title
Sortilin-mediated translocation of mitochondrial ACSL1 impairs adipocyte thermogenesis and energy expenditure in male mice.
- Authors
Yang, Min; Ge, Jing; Liu, Yu-Lian; Wang, Huan-Yu; Wang, Zhi-Han; Li, Dan-Pei; He, Rui; Xie, Yu-Yu; Deng, Hong-Yan; Peng, Xue-Min; Wang, Wen-She; Liu, Jia-Dai; Zhu, Zeng-Zhe; Yu, Xue-Feng; Maretich, Pema; Kajimura, Shingo; Pan, Ru-Ping; Chen, Yong
- Abstract
Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases. Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Here, the authors show that Sortilin in adipose tissues facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation, which controls adipose tissue fatty acid oxidation and substrate fuel selection during beige fat activation.
- Subjects
FATTY acid oxidation; ADIPOSE tissues; COLD adaptation; FUEL switching; BIOCHEMICAL substrates
- Publication
Nature Communications, 2024, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-52218-4