Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A

Jessica Cannavino; Mengle Shao; Yu A. An; Svetlana Bezprozvannaya; Shiuhwei Chen; Jiwoong Kim; Lin Xu; John R. McAnally; Philipp E. Scherer; Ning Liu; Rana K. Gupta; Rhonda Bassel-Duby; Eric N. Olson

doi:10.1073/PNAS.2104650118

Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A

Jessica Cannavino, Mengle Shao, Yu A. An, Svetlana Bezprozvannaya, Shiuhwei Chen, Jiwoong Kim, Lin Xu, John R. McAnally, Philipp E. Scherer, Ning Liu, Rana K. Gupta, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English (US)
Article number	e2104650118
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	118
Issue number	23
DOIs	https://doi.org/10.1073/PNAS.2104650118
State	Published - Apr 29 2021

Keywords

Branched chain amino acids
Brown adipose tissue
Disordered domain protein
RNA binding protein
Thermogenesis

ASJC Scopus subject areas

General

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10.1073/PNAS.2104650118

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Cannavino, J., Shao, M., An, Y. A., Bezprozvannaya, S., Chen, S., Kim, J., Xu, L., McAnally, J. R., Scherer, P. E., Liu, N., Gupta, R. K., Bassel-Duby, R., & Olson, E. N. (2021). Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A. Proceedings of the National Academy of Sciences of the United States of America, 118(23), Article e2104650118. https://doi.org/10.1073/PNAS.2104650118

Cannavino, J, Shao, M, An, YA, Bezprozvannaya, S, Chen, S, Kim, J, Xu, L, McAnally, JR, Scherer, PE , Liu, N, Gupta, RK, Bassel-Duby, R & Olson, EN 2021, 'Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 23, e2104650118. https://doi.org/10.1073/PNAS.2104650118

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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.",

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AU - Xu, Lin

AU - McAnally, John R.

AU - Scherer, Philipp E.

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AU - Gupta, Rana K.

AU - Bassel-Duby, Rhonda

AU - Olson, Eric N.

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AB - 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.

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Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A

Abstract

Keywords

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