BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.

Journal Article (Journal Article)

Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health.

Full Text

Duke Authors

Cited Authors

  • Yoneshiro, T; Wang, Q; Tajima, K; Matsushita, M; Maki, H; Igarashi, K; Dai, Z; White, PJ; McGarrah, RW; Ilkayeva, OR; Deleye, Y; Oguri, Y; Kuroda, M; Ikeda, K; Li, H; Ueno, A; Ohishi, M; Ishikawa, T; Kim, K; Chen, Y; Sponton, CH; Pradhan, RN; Majd, H; Greiner, VJ; Yoneshiro, M; Brown, Z; Chondronikola, M; Takahashi, H; Goto, T; Kawada, T; Sidossis, L; Szoka, FC; McManus, MT; Saito, M; Soga, T; Kajimura, S

Published Date

  • August 2019

Published In

Volume / Issue

  • 572 / 7771

Start / End Page

  • 614 - 619

PubMed ID

  • 31435015

Pubmed Central ID

  • PMC6715529

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/s41586-019-1503-x


  • eng

Conference Location

  • England