High-fat diet up-regulates caveolin-1 expression in aorta of diet-induced obese but not in diet-resistant rats.

OBJECTIVE Caveolin-1 (Cav-1) is considered as a negative regulator of endothelial nitric oxide synthase (eNOS) and influences various cardiovascular functions. The objective of the study is to investigate the effects of high-fat diet on vascular Cav-1 expression and eNOS activities. METHODS Male outbred Sprague-Dawley rats were fed with a high-fat diet for 15 weeks to induce obesity. The diet-induced obese (DIO) rats were then divided into two groups. One group (DIO-LF) was fed a normal diet and another group (DIO-HF) along with diet-resistance (DR) rats were fed a high-fat diet for 8 more weeks. Cav-1 expression was determined using reverse transcription (RT)-PCR, Western blotting, and immunohistochemistry techniques. NOS activities were assessed using Griess reagents. Protein kinase B (PKB/Akt) and eNOS expression and phosphorylation were determined by Western blotting. RESULTS A high-fat diet up-regulated Cav-1 and down-regulated eNOS expression in aorta of DIO rats, but not in that of DR rats. These effects were reversed in DIO rats after switching to a low-fat diet for 8 weeks. Decreased NOS activities in aortas were observed in DIO rats, but not in DR rats. Phosphorylation of PKB/Akt and eNOS (Ser1177) were enhanced in aortas of DIO rats of both DIO-HF and DIO-LF groups. CONCLUSION These findings suggest that the decrease of vascular NOS activities in rats fed a high-fat diet were due, at least in part, to the up-regulation of Cav-1 expression.