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Metformin Affects Cardiac Arachidonic Acid Metabolism and Cardiac Lipid Metabolite Storage in a Prediabetic Rat Model

D. Miklankova, I. Markova, M. Hüttl, I. Zapletalova, M. Poruba, H. Malinska

. 2021 ; 22 (14) : . [pub] 20210719

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc21025335

Grant support
IN 00023001 Ministerstvo Zdravotnictví Ceské Republiky
IGA_LF_2021_013 Ministerstvo Zdravotnictví Ceské Republiky

Metformin can reduce cardiovascular risk independent of glycemic control. The mechanisms behind its non-glycemic benefits, which include decreased energy intake, lower blood pressure and improved lipid and fatty acid metabolism, are not fully understood. In our study, metformin treatment reduced myocardial accumulation of neutral lipids-triglycerides, cholesteryl esters and the lipotoxic intermediates-diacylglycerols and lysophosphatidylcholines in a prediabetic rat model (p < 0.001). We observed an association between decreased gene expression and SCD-1 activity (p < 0.05). In addition, metformin markedly improved phospholipid fatty acid composition in the myocardium, represented by decreased SFA profiles and increased n3-PUFA profiles. Known for its cardioprotective and anti-inflammatory properties, metformin also had positive effects on arachidonic acid metabolism and CYP-derived arachidonic acid metabolites. We also found an association between increased gene expression of the cardiac isoform CYP2c with increased 14,15-EET (p < 0.05) and markedly reduced 20-HETE (p < 0.001) in the myocardium. Based on these results, we conclude that metformin treatment reduces the lipogenic enzyme SCD-1 and the accumulation of the lipotoxic intermediates diacylglycerols and lysophosphatidylcholine. Increased CYP2c gene expression and beneficial effects on CYP-derived arachidonic acid metabolites in the myocardium can also be involved in cardioprotective effect of metformin.

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