Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
Program in Molecular Medicine; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
Brown adipose tissue (BAT) is a therapeutic target for metabolic diseases; thus, understanding its metabolic circuitry is clinically important. Many studies of BAT compare rodents mildly cold to those severely cold. Here, we compared BAT remodeling between thermoneutral and mild-cold-adapted mice, conditions more relevant to humans. Although BAT is renowned for catabolic beta-oxidative capacity, we find paradoxically that the anabolic de novo lipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates with Ucp1 expression. The regulation and function of adipocyte DNL and its association with thermogenesis are not understood. We provide evidence suggesting that AKT2 drives DNL in adipocytes by stimulating ChREBPbeta transcriptional activity and that cold induces the AKT2-ChREBP pathway in BAT to optimize fuel storage and thermogenesis. These data provide insight into adipocyte DNL regulation and function and illustrate the metabolic flexibility of thermogenesis.
DOI of Published Version
Cell Metab. 2018 Jan;27(1):195-209.e6. doi: 10.1016/j.cmet.2017.10.008.10.1016/j.cmet.2017.10.008. Link to article on publisher's site
Sanchez-Gurmaches, Joan; Tang, Yuefeng; Jespersen, Naja Zenius.; Wallace, Martina; Calejman, Camila Martinez; Gujja, Sharvari; Li, Huawei; Edwards, Yvonne J. K.; Wolfrum, Christian; Metallo, Christian M.; Nielsen, Soren; Scheele, Camilla; and Guertin, David A., "Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis" (2018). UMass Metabolic Network Publications. 141.