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

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Abstract

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 (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. 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.

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Bai, F., Liu, Y., Tu, T., Li, B., Xiao, Y., Ma, Y., … Liu, Q. (2019). Metformin regulates lipid metabolism in a canine model of atrial fibrillation through AMPK/PPAR-α/VLCAD pathway. Lipids in Health and Disease, 18(1). https://doi.org/10.1186/s12944-019-1059-7

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