摘要
向心性肥胖、高血压、高血脂症为特征的代谢综合征,增加了心血管疾病、2型糖尿病、非酒精性脂肪肝等代谢性疾病的发病率和死亡率。众所周知,胰岛素抵抗,尤其是肝胰岛素抵抗是代谢综合征的危险因素。目前研究表明,肝脏脂肪酸积累可通过糖异生、脂肪生成、慢性炎症、氧化应激、内质网应激、胰岛素信号通路受损等途径引起肝脏胰岛素抵抗。脂肪酸在线粒体中进行的β氧化是脂肪酸的主要代谢途径,线粒体功能障碍已被证实与肝脂肪酸异常诱导的肝胰岛素抵抗的发生密切相关。线粒体自噬是细胞的一种分解代谢过程,选择性降解受损的线粒体,以逆转线粒体功能障碍,保持线粒体动力学功能。因此,线粒体自噬可以促进线粒体脂肪酸氧化,抑制肝脏脂肪酸积累,改善肝脏胰岛素抵抗。本文先回顾了关于线粒体自噬和肝胰岛素抵抗之间关系的研究进展,此外还强调了线粒体自噬在肝脏胰岛素抵抗和代谢综合征治疗中的潜在价值。
Metabolic syndrome,characterized by centralobesity,hypertension,bycentralobesity,hypertension,and hyperlipidemia,increases the incidence and mortality of cardiovascular disease,type 2 diabetes,nonalcoholic fatty liver disease,and other metabolic diseases.It is well known that insulin resistance,especially hepatic insulin resistance,is a risk factor for metabolic syndrome.Current research has shown that the accumulation of hepatic fatty acid can cause hepatic insulin resistance through increased gluconeogenesis,lipogenesis,chronic inflammation,oxidative stress and endoplasmic reticulum stress,and impaired insulin signal pathway.Mitochondria are the major sites of fatty acidβ-oxidation,which is the major degradation mechanism of fatty acids.Mitochondrial dysfunction has been shown to be involved in the development of hepatic fatty acid-induced hepatic insulin resistance.Mitochondrial autophagy(mitophagy),a catabolic process,selectively degrades damaged mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial dynamics and function.Therefore,mitophagy can promote mitochondrial fatty acid oxidation to inhibit hepatic fatty acid accumulation and improve hepatic insulin resistance.Here,we review advances in our understanding of the relationship between mitophagy and hepatic insulin resistance.Additionally,we also highlight the potential value of mitophagy in the treatment of hepatic insulin resistance and metabolic syndrome.
作者
全海燕
江兴
何璐
QUAN Haiyan;JIANG Xing;HE Lu(School of Medicine and Pharmacy,Hunan Polytechnic of Environment and Biology,Hengyang 421005,Hunan,China;Department of Pharmacy,The Second Affiliated Hospital of Nanhua University,Hengyang 421000 Hunan,China;Department of Neurosurgery,The First Affiliated Hospital of Nanhua University,Hengyang 421001,Hunan,China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2022年第2期198-204,共7页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金(81803535)
湖南省自然科学基金(2018JJ6070)
衡阳市科技计划项目(2020jh042693)。
