支链氨基酸代谢:代谢性疾病的病理生理机制和治疗干预。

IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Obesity Reviews Pub Date : 2024-10-25 DOI:10.1111/obr.13856
Shama Mansoori, Melody Yuen-Man Ho, Kelvin Kwun-Wang Ng, Kenneth King-Yip Cheng
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引用次数: 0

摘要

支链氨基酸(BCAAs),包括亮氨酸、异亮氨酸和缬氨酸,是维持生理功能和代谢平衡所必需的物质。然而,支链氨基酸的长期升高会导致代谢性疾病,如肥胖、2 型糖尿病(T2D)和代谢相关性脂肪肝(MAFLD)。脂肪组织、骨骼肌和肝脏是三大代谢组织,不仅负责控制血糖、血脂和能量平衡,还负责维持 BCAA 的平衡。在肥胖和糖尿病条件下,不同的致病因素,如促炎细胞因子、脂肪毒性、脂肪连素和过氧化物酶体增殖激活受体γ(PPARγ)的减少,会破坏 BCAA 的代谢,导致 BCAA 及其下游代谢产物在代谢组织和血液循环中过度积累。从机理上讲,BCAAs 和/或其下游代谢产物,如支链酮酸(BCKAs)和 3-羟基异丁酸(3-HIB),会损害胰岛素信号传导,抑制脂肪生成,诱发炎症反应,并在代谢组织中引起脂肪毒性,从而导致多种代谢紊乱。在这篇综述中,我们总结了有关三大代谢组织--脂肪组织、骨骼肌和肝脏--对 BCAA 平衡的代谢调节的最新研究,以及 BCAA 代谢失调如何影响这些活跃代谢组织中的葡萄糖、脂质和能量平衡。我们还总结了恢复正常 BCAA 代谢的治疗方法,以治疗代谢性疾病。
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Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.

Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential for maintaining physiological functions and metabolic homeostasis. However, chronic elevation of BCAAs causes metabolic diseases such as obesity, type 2 diabetes (T2D), and metabolic-associated fatty liver disease (MAFLD). Adipose tissue, skeletal muscle, and the liver are the three major metabolic tissues not only responsible for controlling glucose, lipid, and energy balance but also for maintaining BCAA homeostasis. Under obese and diabetic conditions, different pathogenic factors like pro-inflammatory cytokines, lipotoxicity, and reduction of adiponectin and peroxisome proliferator-activated receptors γ (PPARγ) disrupt BCAA metabolism, leading to excessive accumulation of BCAAs and their downstream metabolites in metabolic tissues and circulation. Mechanistically, BCAAs and/or their downstream metabolites, such as branched-chain ketoacids (BCKAs) and 3-hydroxyisobutyrate (3-HIB), impair insulin signaling, inhibit adipogenesis, induce inflammatory responses, and cause lipotoxicity in the metabolic tissues, resulting in multiple metabolic disorders. In this review, we summarize the latest studies on the metabolic regulation of BCAA homeostasis by the three major metabolic tissues-adipose tissue, skeletal muscle, and liver-and how dysregulated BCAA metabolism affects glucose, lipid, and energy balance in these active metabolic tissues. We also summarize therapeutic approaches to restore normal BCAA metabolism as a treatment for metabolic diseases.

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来源期刊
Obesity Reviews
Obesity Reviews 医学-内分泌学与代谢
CiteScore
19.30
自引率
1.10%
发文量
130
审稿时长
1 months
期刊介绍: Obesity Reviews is a monthly journal publishing reviews on all disciplines related to obesity and its comorbidities. This includes basic and behavioral sciences, clinical treatment and outcomes, epidemiology, prevention and public health. The journal should, therefore, appeal to all professionals with an interest in obesity and its comorbidities. Review types may include systematic narrative reviews, quantitative meta-analyses and narrative reviews but all must offer new insights, critical or novel perspectives that will enhance the state of knowledge in the field. The editorial policy is to publish high quality peer-reviewed manuscripts that provide needed new insight into all aspects of obesity and its related comorbidities while minimizing the period between submission and publication.
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