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研究揭示棕色脂肪代谢新机制
2019-08-22 13:43

美国加州大学旧金山分校Shingo Kajimura研究组发现棕色脂肪中的BCAA分解代谢通过SLC25A44控制能量稳态。该项研究成果于2019年8月21在线发表在《自然》杂志上。

据该研究组报道,当暴露在寒冷环境时,棕色脂肪组织(BAT)能够活跃的利用线粒体中的BCAA进行产热以及促进小鼠和人类的全身性的BCAA清除。 反过来,BCAA分解代谢中的BAT特异性缺陷减弱了全身性的BCAA清除以及BAT的氧化和产热,从而导致饮食诱导的肥胖和葡萄糖耐受不良。在调控机制上,BAT中的活跃的BCAA分解代谢由SLC25A44介导,并将BCAA转运到线粒体中。他们的研究结果表明,BAT作为关键的代谢过滤器,通过SLC25A44调控BCAA清除,从而有助于代谢健康的改善。

研究人员表示,支链氨基酸(BCAA;缬氨酸、亮氨酸和异亮氨酸)补充通常是有益的能量消耗;然而,增加BCAA的循环水平与肥胖和糖尿病有关。这种悖论的机制仍不清楚。

附:英文原文

Title: BCAA catabolism in brown fat controls energy homeostasis through SLC25A44

Author: Takeshi Yoneshiro, Qiang Wang, Kazuki Tajima, Mami Matsushita, Hiroko Maki, Kaori Igarashi, Zhipeng Dai, Phillip J. White, Robert W. McGarrah, Olga R. Ilkayeva, Yann Deleye, Yasuo Oguri, Mito Kuroda, Kenji Ikeda, Huixia Li, Ayano Ueno, Maki Ohishi, Takamasa Ishikawa, Kyeongkyu Kim, Yong Chen, Carlos Henrique Sponton, Rachana N. Pradhan, Homa Majd, Vanille Juliette Greiner, Momoko Yoneshiro, Zachary Brown, Maria Chondronikola, Haruya Takahashi, Tsuyoshi Goto, Teruo Kawada, Labros Sidossis, Francis C. Szoka, Michael T. McManus, Masayuki Saito, Tomoyoshi Soga, Shingo Kajimura

Issue&Volume: 2019-08-21

Abstract: 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.

DOI: 10.1038/s41586-019-1503-x

Source:https://www.nature.com/articles/s41586-019-1503-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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