Effect of gemfibrozil on adipose tissue and muscle lipoprotein lipase.
To better understand the mechanism of action of gemfibrozil on plasma triglycerides, lipoprotein lipase (LPL) concentration was measured in adipose tissue and muscle of 16 hypertriglyceridemic patients before and after treatment with gemfibrozil for 6 weeks. The patients were divided into three groups based on clinical criteria as follows: group 1, hypertriglyceridemia without secondary factors; group 2, hypertriglyceridemia with diabetes; and group 3, hypertriglyceridemia with renal insufficiency. LPL activity, immunoreactive mass, synthetic rate, and mRNA levels were measured in the adipose tissue samples, and LPL activity and mass in the muscle samples. Serum triglyceride levels were decreased by 46% by gemfibrozil, and patients demonstrated no change in diet, weight, or glycohemoglobin during the 6 weeks of treatment. Despite the decrease of blood triglyceride levels, there was no significant change in any measure of LPL either in adipose tissue or muscle. Although several patients demonstrated increases in muscle LPL activity, these changes were inconsistent and not statistically significant. Because there was no significant change in LPL, we conclude that gemfibrozil in these patients decreased circulating triglyceride levels predominantly by decreasing hepatic very-low-density lipoprotein (VLDL) secretion.
Simsolo
R B
RB
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Ong
J M
JM
Kern
P A
PA
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015248:Gemfibrozil / Q000494:pharmacology* / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood
D012333:RNA, Messenger; D014280:Triglycerides; D008071:Lipoprotein Lipase; D015248:Gemfibrozil