Metformin regulates lipid metabolism in a canine model of atrial fibrillation through AMPK/PPAR-/VLCAD pathway

被引：58

作者：

Bai, Fan ^{[1
]}

Liu, Yaozhong ^{[1
]}

Tu, Tao ^{[1
]}

Li, Biao ^{[1
]}

Xiao, Yichao ^{[1
]}

Ma, Yingxu ^{[1
]}

Qin, Fen ^{[1
]}

Xie, Jing ^{[1
]}

Zhou, Shenghua ^{[1
]}

Liu, Qiming ^{[1
]}

机构：

[1] Cent S Univ, Xiangya Hosp 2, Cardiac Catheterizat Lab, Dept Cardiol, 139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China

来源：

LIPIDS IN HEALTH AND DISEASE | 2019年 / 18卷

基金：

中国国家自然科学基金;

关键词：

Atrial fibrillation; Lipid metabolism; AMPK; Metformin; ACTIVATED PROTEIN-KINASE; PPAR-ALPHA AGONIST; CARDIAC-HYPERTROPHY; RECEPTOR-ALPHA; PROTEOMIC ANALYSIS; DISEASE PATIENTS; POTENTIAL ROLE; HEART; AMPK; FENOFIBRATE;

D O I：

10.1186/s12944-019-1059-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

BackgroundAtrial lipid metabolic remodeling is critical for the process of atrial fibrillation (AF). Abnormal Fatty acid (FA) metabolism in cardiomyocytes is involved in the pathogenesis of AF. MET (Metformin), an AMPK (AMP-activated protein kinase) activator, has been found to be associated with a decreased risk of AF in patients with type 2 diabetes. However, the specific mechanism remains unknown.MethodsFifteen mongrel dogs were divided into three groups: SR, ARP (pacing with 800 beats/min for 6h), ARP plus MET (treated with MET (100mg/kg/day) for two weeks before pacing). We assessed metabolic factors, speed limiting enzymes circulating biochemical metabolites (substrates and products), atrial electrophysiology and accumulation of lipid droplets.ResultsThe expression of AMPK increased in the ARP group and significantly increased in the MET+ARP group comparing to the SR group. In the ARP group, the expressions of PPAR?PGC-1 and VLCAD were down-regulated, while the concentration of free fatty acid and triglyceride and the lipid deposition in LAA (left atrial appendage) increased. Moreover, AERP and AERPd have also been found abnormally in this process. Pretreatment with MET before receiving ARP reversed the alterations aforementioned.ConclusionsThe FA metabolism in LAA is altered in the ARP group, mainly characterized by the abnormal expression of the rate-limiting enzyme. Metformin reduces lipid accumulation and promotes -oxidation of FA in AF models partially through AMPK/PPAR-/VLCAD pathway. Our study indicates that MET may inhibit the FA lipid metabolic remodeling in AF.

引用

页数：9

共 51 条

[1] Effect of glucose-insulin-potassium infusion on plasma free fatty acid concentrations in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction [J].