Metformin regulates lipid metabolism in a canine model of atrial fibrillation through AMPK/PPAR-alpha/VLCAD pathway.
Metformin regulates lipid metabolism in a canine model of atrial fibrillation through AMPK/PPAR-alpha/VLCAD pathway.
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DOI：
10.1186/s12944-019-1059-7
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发表时间：
2019
影响因子：
4.5
通讯作者：
Qiming Liu
中科院分区：
文献类型：
--
作者：
Fan Bai;Yaozhong Liu;Tao Tu;Biao Li;Yichao Xiao;Yingxu Ma;Fen Qin;Jing Xie;Shenghua Zhou;Qiming Liu
Background: Atrial 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 (AMPactivated 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..Methods: Fifteen mongrel dogs were divided into three groups: SR, ARP (pacing with 800 beats/min for 6 h), ARP.plus MET (treated with MET (100 mg/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..Results: The 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 PPARα、PGC-1α 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..Conclusions: The 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 β-oxidation of FA.in AF models partially through AMPK/PPAR-α/VLCAD pathway. Our study indicates that MET may inhibit the.FA lipid metabolic remodeling in AF.
