@article{5d299d88d20d4f9484e2f43d1c24f451,
title = "Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A",
abstract = "Homeothermic vertebrates produce heat in cold environments through thermogenesis, in which brown adipose tissue (BAT) increases mitochondrial oxidation along with uncoupling of the electron transport chain and activation of uncoupling protein 1 (UCP1). Although the transcription factors regulating the expression of UCP1 and nutrient oxidation genes have been extensively studied, only a few other proteins essential for BAT function have been identified. We describe the discovery of FAM195A, a BAT-enriched RNA binding protein, which is required for cold-dependent thermogenesis in mice. FAM195A knockout (KO) mice display whitening of BAT and an inability to thermoregulate. In BAT of FAM195A KO mice, enzymes involved in branched-chain amino acid (BCAA) metabolism are down-regulated, impairing their response to cold. Knockdown of FAM195A in brown adipocytes in vitro also impairs expression of leucine oxidation enzymes, revealing FAM195A to be a regulator of BCAA metabolism and a potential target for metabolic disorders.",
keywords = "Branched chain amino acids, Brown adipose tissue, Disordered domain protein, RNA binding protein, Thermogenesis",
author = "Jessica Cannavino and Mengle Shao and An, {Yu A.} and Svetlana Bezprozvannaya and Shiuhwei Chen and Jiwoong Kim and Lin Xu and McAnally, {John R.} and Scherer, {Philipp E.} and Ning Liu and Gupta, {Rana K.} and Rhonda Bassel-Duby and Olson, {Eric N.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank Jose Cabrera for graphics, John Shelton for help with histology, Laurent Gautron for providing probes and apparatus for electromyography experiments, Joshua Heinrich for assistance in performing running experiment, Alex Mireault for performing grip strength assay, Wei Tan for performing echocardiograms, and Kenian Chen for analysis of published ChIP-seq data. We also thank Kedryn Baskin and Christine Kusminski for helpful discussion. We thank the Genomics and Microarray Core for RNA-seq, the Histo Pathology Core for histological analysis and expertise, the University of Texas Southwestern Proteomics Core for mass spectrometry, and the University of Texas Southwestern Metabolic Phenotyping Core for the liquid chromatography with tandem mass spectrometry analysis of free amino acids in plasma samples. This work was supported by funds from NIH Grants HL130253, AR071980, and AR-067294; Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center Grant P50HD087351; Career Development Award 19CDA34670007 from American Heart Association and the Harry S. Moss Heart Trust (to M.S.); NIH, National Institute of Diabetes and Digestive and Kidney Diseases Grant K01-DK125447 (to Y.A.A.); NIH, National Institute of Diabetes and Digestive and Kidney Diseases Grants R01 DK104789 (to R.K.G.), R56 DK119163 (to R.K.G.), and R01 DK119163 (to R.K.G.); and Robert A. Welch Foundation Grant 1-0025 (to E.N.O.). Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved.",
year = "2021",
month = apr,
day = "29",
doi = "10.1073/PNAS.2104650118",
language = "English (US)",
volume = "118",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "23",
}