Metaformin: an antiatherosclerotic agent modifying very low density lipoproteins in rabbits.
The composition of very low density lipoproteins (VLDL: d less than 1.019) of New Zealand male rabbits reciving cholesterol (2 g/day) and metformin (135 mg/kg/day) is investigated. These rabbits, while showing only a slight reduction of plasma cholesterol levels, as compared to cholesterol-fed (h.c.) animals, show a marked decrease of the aortic cholesterol esters and atheromatous process. VLDL from the cholesterol + metformin group (h.c. + met), as compared to the h.c. animals, are homogenous in size and not separable into VLDL-1 and VLDL-2 subfractions by Sepharose 4B chromatography. These findings are confirmed by electron microscopy, which shows homogeneity of particle size, as well a decreased tendency of h.c. + met VLDL to aggregate. Chemical composition of h.c. + met VLDL is characterized by increased triglycerides and phospholipids, while the percentage of cholesterol esters is not significantly decreased. Phospholipid distribution of h.c. + met VLDL shows a significant decrease of sphingomyelin and increased phosphatidylinositol, the latter both as compared to h.c. and control VLDL. Apoprotein pattern of h.c. + met VLDL in polyacrylamide gels shows a relative increase of peptides with C mobility and a decrease of proteins corresponding to the arg-rich peptides. These findings exemplify a case of altered lipoprotein composition and decreased atheromatosis, in the presence of marked hypercholesteremia.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001053:Apolipoproteins / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006937:Hypercholesterolemia / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000032:analysis / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008854:Microscopy, Electron; D010316:Particle Size; D010743:Phospholipids / Q000378:metabolism; D011817:Rabbits
D001053:Apolipoproteins; D001786:Blood Glucose; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D010743:Phospholipids; D008687:Metformin; D002784:Cholesterol