The Molecular Mechanisms of Metformin's Action on Blood Lipid Profile in Diabetic Patients
Abstract
In this paper, we review the literature regarding metformin's action on blood lipid concentrations in metformin-treated diabetic patients. Published data indicate that metformin reduces serum total cholesterol (T-C), LDL-cholesterol (LDL-C) and triacylglycerol (TAG) concentrations and raises serum HDL-cholesterol (HDL-C) concentrations in diabetic patients. The beneficial effect of metformin on serum lipid profiles in diabetic patients can result from (a) its action on AMP-activated protein kinase, which inhibits lipogenesis and cholesterol synthesis and stimulates fatty acid oxidation; (b) decreased plasma TAG concentrations, via promoting VLDL-TAG clearance by brown adipose tissue; (c) the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression, affecting lipid profile in diabetic patients; (d) the inhibition of the expression of genes encoding proprotein convertase subtilisin/kexin 9 (PCSK9) and lipogenic enzymes; (e) the downregulation of carbohydrate-response element-binding protein (ChREBP), which affects liver TAG and cholesterol synthesis from acetate formed by gut microbiota; (f) the inhibition of angiopoietin-like 3 protein (ANGPTL3) gene expression, and consequent effects on plasma TAG concentrations; (g) the activation of AMPK, which inhibits LXRα activity; and (h) reverse cholesterol transport. In conclusion, one can assume that beyond its primary antihyperglycemic effect, metformin exerts pleiotropic effects that modulate lipid…
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