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Cold-Activated Lipid Dynamics in Adipose Tissue Highlights a Role for Cardiolipin in Thermogenic Metabolism

Cell Reports. 2018 Jul 17;24(3):781-790

Matthew D. Lynes, Farnaz Shamsi, Elahu Gosney Sustarsic, Luiz O. Leiria, Chih-Hao Wang, Sheng-Chiang Su, Tian Lian Huang, Fei Gao, Niven R. Narain, Emily Y. Chen, Aaron M. Cypess,Tim J. Schulz, Zachary Gerhart- Hines, Michael A. Kiebish,Yu-Hua Tseng

Thermogenic fat expends energy during cold for temperature homeostasis, and its activity regulates nutrient metabolism and insulin sensitivity. We measured cold-activated lipid landscapes in circulation and in adipose tissue by liquid chromatography coupled mass spectrometry (LC-MS). Interestingly, plasma samples from cold exposed humans and mice showed increases in phospholipids. In adipose tissue, among the over 2,000 lipid species profiled, we identified the biosynthetic pathway of the mitochondrial lipid cardiolipin (CL), which is a product of phospholipids, was coordinately activated in brown and beige fat by cold or genetic activation. Expression of the enzyme cardiolipin synthase 1 (CRLS1) was selectively elevated in mouse and human brown fat compared to white fat and was significantly increased in by cold. CRLS1 knockdown blocked mitochondrial biogenesis in human brown adipocytes. Together, these data provide a comprehensive lipid bio-signature of thermogenic fat activation in blood and tissue and suggest new pathways regulated by cold exposure.

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