Fenofibrate lowers adiposity and corrects metabolic abnormalities, but only partially restores endothelial function in dietary obese rats.
In humans, dietary-induced obesity markedly increases plasma lipid profile and impairs vascular function leading to increased incidence of cardiovascular events. We have recently reported that chronic withdrawal of obesity-inducing diet attenuates obesity and completely corrects endothelial function. The aim of this study was to investigate whether fenofibrate-induced decrease in adiposity would also correct vascular function in the presence of obesity-inducing diet. Wistar rats were fed with either standard laboratory chow (lean, n = 9) or given a highly palatable diet (diet-fed, n = 18) for 15 weeks. After 7 weeks, half of the diet-fed group was treated with fenofibrate (fenofibrate-treated, n = 9) for 8 weeks before being sacrificed. Untreated diet-fed (n = 9) rats had significantly higher body weight, total fat mass (by up to two-fold, p < 0.001 for both), and raised fasting plasma levels of insulin, leptin and triglycerides (up to 110%; p < 0.001), but not glucose or nonesterified fatty acids (NEFA) than both lean control and fenofibrate-treated groups. Resistance mesenteric arteries responses to KCl- and noradrenaline-induced vasoconstriction were similar in all three groups. However, compared with lean controls, endothelium-dependent vasorelaxation responses were shifted to the right in both untreated and fenofibrate-treated diet-fed groups. Fenofibrate treatment improved endothelium-dependent vasorelaxation at only high carbamycholine concentrations (10 microM). There were no differences in endothelium-independent vasorelaxation between the three groups. These results indicate that, in the presence of obesity-inducing diet, fenofibrate markedly reverses obesity and corrects insulin resistance and lipid profile, but it only has a limited beneficial effect on vascular function. Therefore, it seems that diet component rather than obesity per se plays a key role in the genesis of vascular abnormalities.
Naderali
Ebrahim K
EK
Neuroendocrine and Obesity Biology Unit, Department of Medicine, University of Liverpool, Daulby Street, Liverpool L69 3GA, UK. naderali@liverpool.ac.uk
Fatani
Sameer
S
Williams
Gareth
G
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004032:Diet; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000502:physiology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D020738:Leptin; D014280:Triglycerides; D011345:Fenofibrate