장철순 (University of California Irvine)

한빛사논문

조회394

University of California Irvine

CV File 288 kb

Nat Metab., 2023 Jun 19 | https://doi.org/10.1038/s42255-023-00825-8 Quantitative analysis of metabolic fluxes in brown fat and skeletal muscle during thermogenesis

Grace Park^{# 1}, John A Haley ^{# 2}, Johnny Le ^{# 1}, Su Myung Jung ^{# 3}, Timothy P Fitzgibbons ⁴, Ekaterina D Korobkina ², Huawei Li ², Shelagh M Fluharty ², Qingbo Chen², Jessica B Spinelli ², Chinmay M Trivedi ^4,5,6, Cholsoon Jang ^1*, David A Guertin^2*

¹Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
²Program in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA.
³Department of Biological Sciences, Sungkyunkwan University, Suwon, South Korea.
⁴Division of Cardiovascular Medicine, Department of Medicine, UMass Chan Medical School, Worcester, MA, USA.
⁵Department of Molecular, Cell and Cancer Biology, UMass Chan Medical School, Worcester, MA, USA.
⁶Li-Weibo Institute for Rare Diseases Research, UMass Chan Medical School, Worcester, MA, USA.

^#These authors contributed equally: Grace Park, John A. Haley, Johnny Le, Su Myung Jung.
^*Corresponding authors : Correspondence to Cholsoon Jang or David A. Guertin.

Abstract

Adaptive thermogenesis by brown adipose tissue (BAT) dissipates calories as heat, making it an attractive anti-obesity target. Yet how BAT contributes to circulating metabolite exchange remains unclear. Here, we quantified metabolite exchange in BAT and skeletal muscle by arteriovenous metabolomics during cold exposure in fed male mice. This identified unexpected metabolites consumed, released and shared between organs. Quantitative analysis of tissue fluxes showed that glucose and lactate provide ~85% of carbon for adaptive thermogenesis and that cold and CL316,243 trigger markedly divergent fuel utilization profiles. In cold adaptation, BAT also dramatically increases nitrogen uptake by net consuming amino acids, except glutamine. Isotope tracing and functional studies suggest glutamine catabolism concurrent with synthesis via glutamine synthetase, which avoids ammonia buildup and boosts fuel oxidation. These data underscore the ability of BAT to function as a glucose and amino acid sink and provide a quantitative and comprehensive landscape of BAT fuel utilization to guide translational studies.

논문정보

형식Research article
게재일2023년 06월 (BRIC 등록일 2023-06-21)
연구진국내+국외 연구진
분야 생명과학 > 생화학

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