CD36 inhibitors reduce postprandial hypertriglyceridemia and protect against diabetic dyslipidemia and atherosclerosis.
CD36 is recognized as a lipid and fatty acid receptor and plays an important role in the metabolic syndrome and associated cardiac events. The pleiotropic activity and the multiple molecular associations of this scavenger receptor with membrane associated molecules in different cells and tissues have however questioned its potential as a therapeutic target. The present study shows that it is possible to identify low molecular weight chemicals that can block the CD36 binding and uptake functions. These inhibitors were able to reduce arterial lipid deposition, fatty acid intestinal transit, plasma concentration of triglycerides and glucose, to improve insulin sensitivity, glucose tolerance and to reduce the plasma concentration of HbAc1 in different and independent rodent models. Correlation between the anti-CD36 activity of these inhibitors and the known pathophysiological activity of this scavenger receptor in the development of atherosclerosis and diabetes were observed at pharmacological doses. Thus, CD36 might represent an attractive therapeutic target.
INSERM U1060, CarMeN laboratory, Lyon University, INSA-Lyon, IMBL Villeurbanne, France.
Alain
A
Geloen
Lionel
L
Helin
Benjamine
B
Geeraert
Eric
E
Malaud
Paul
P
Holvoet
Gerard
G
Marguerie
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control*; D001562:Benzimidazoles; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D048909:Diabetes Complications / Q000517:prevention & control*; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D019518:Postprandial Period; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*
C576728:AP5055; C576727:AP5258; D001562:Benzimidazoles; D018955:CD36 Antigens; D013876:Thiophenes