Brown fat thermogenesis and branched-chain amino acids in metabolic disease.

IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Endocrine journal Pub Date : 2024-02-28 Epub Date: 2023-11-09 DOI:10.1507/endocrj.EJ23-0205
Zachary Brown, Takeshi Yoneshiro
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Abstract

Since the 1960s, researchers have recognized an association between elevated plasma branched chain amino acids (BCAA) and metabolic disease, including type 2 diabetes mellitus and obesity, but the cause for it remained poorly understood. Recent advances in metabolomics, advanced imaging techniques, and genetic analyses over the past decade have enabled newfound insights into the mechanism of BCAA metabolic dysregulation across a variety of peripheral tissues and its impact on metabolic disease, suggesting a key role for brown adipose tissue (BAT) in determining BCAA metabolic homeostasis. Previous investigations into BAT have emphasized fatty acids and glucose as substrates for BAT thermogenesis. Here, we address the importance of BAT in systemic BCAA metabolism, driven via the newly identified mitochondrial BCAA carrier (MBC), as well as the impact of BAT-driven BCAA clearance on glucose homeostasis and metabolic disease. The newly identified MBC offers new therapeutic avenues by which BAT activity may be enhanced to improve metabolic and cardiovascular health, as well as other diseases in which increases of circulating BCAA may play a role in pathogenicity.

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代谢性疾病中的棕色脂肪产热和支链氨基酸。
自20世纪60年代以来,研究人员已经认识到血浆支链氨基酸(BCAA)升高与代谢性疾病(包括2型糖尿病和肥胖)之间的联系,但其原因尚不清楚。在过去的十年里,代谢组学、先进的成像技术和遗传分析的最新进展使人们能够对各种外周组织中BCAA代谢失调的机制及其对代谢疾病的影响有新的见解,这表明棕色脂肪组织(BAT)在确定BCAA代谢稳态中发挥着关键作用。先前对BAT的研究强调脂肪酸和葡萄糖是BAT产热的底物。在这里,我们讨论了BAT在通过新发现的线粒体BCAA载体(MBC)驱动的系统BCAA代谢中的重要性,以及BAT驱动的BCAA清除对葡萄糖稳态和代谢疾病的影响。新发现的MBC提供了新的治疗途径,通过这些途径可以增强BAT活性,以改善代谢和心血管健康,以及循环BCAA增加可能在致病性中发挥作用的其他疾病。
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来源期刊
Endocrine journal
Endocrine journal 医学-内分泌学与代谢
CiteScore
4.30
自引率
5.00%
发文量
224
审稿时长
1.5 months
期刊介绍: Endocrine Journal is an open access, peer-reviewed online journal with a long history. This journal publishes peer-reviewed research articles in multifaceted fields of basic, translational and clinical endocrinology. Endocrine Journal provides a chance to exchange your ideas, concepts and scientific observations in any area of recent endocrinology. Manuscripts may be submitted as Original Articles, Notes, Rapid Communications or Review Articles. We have a rapid reviewing and editorial decision system and pay a special attention to our quick, truly scientific and frequently-citable publication. Please go through the link for author guideline.
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