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
{"title":"支链氨基酸代谢:代谢性疾病的病理生理机制和治疗干预。","authors":"Shama Mansoori, Melody Yuen-Man Ho, Kelvin Kwun-Wang Ng, Kenneth King-Yip Cheng","doi":"10.1111/obr.13856","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":216,"journal":{"name":"Obesity Reviews","volume":null,"pages":null},"PeriodicalIF":8.0000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.\",\"authors\":\"Shama Mansoori, Melody Yuen-Man Ho, Kelvin Kwun-Wang Ng, Kenneth King-Yip Cheng\",\"doi\":\"10.1111/obr.13856\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":216,\"journal\":{\"name\":\"Obesity Reviews\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.0000,\"publicationDate\":\"2024-10-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Obesity Reviews\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/obr.13856\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Obesity Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/obr.13856","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
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.
期刊最新文献
Longer-term effects of intermittent fasting on body composition and cardiometabolic health in adults with overweight and obesity: A systematic review and meta-analysis. Identifying behavior change techniques (BCTs) in responsive feeding interventions to prevent childhood obesity-A systematic review. Effects of mindfulness-based interventions on obesogenic eating behaviors: A systematic review and meta-analysis. Barriers and enablers to effective weight management for people living with overweight and obesity: A rapid scoping review. Molecular mechanisms of the obesity associated with Bardet-Biedl syndrome: An update.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1