The Increase in Hepatic Uncoupling by Fenofibrate Contributes to a Decrease in Adipose Tissue in Obese Rats

Fenofibrate is a drug that has been suggested to inhibit weight gain by increasing the catabolism of fatty acid in the hepatic mitochondria. We hypothesized that fenofibrate induces an increase in energy expenditure in the hepatic mitochondria, which results in the reduction of adipose tissue. In this study we measured hepatic uncoupling protein (UCP)-2, -3, core temperatures and abdominal fat composition with MRI in Otsuka Long-Evans Tokushima Fatty rats. The fenofibrate group (n=7) was fed fenofibrate (320 mg/kg) mixed chow. The control group (n=7) was fed chow only. The body weight (531.6±7.6 g) of the fenofibrate group was significantly lower than that (744.3±14.9 g) of the control group (p<0.005). The areas of visceral and subcutaneous fat in the fenofibrate group (11.0±0.9 cm(2), 4.2±0.3 cm(2)) were significantly less than those in the control group (21.0±0.7 cm(2), 7.4±0.4 cm(2)) (p=0.046, respectively). The esophageal and rectal temperatures of the fenofibrate group (37.7±0.1℃, 33.1±0.2℃) were significantly higher than those of the control group (37.3±0.1℃, 32.2±0.1℃) (p=0.025, p=0.005). There was de novo expression of UCP-3 in the liver of the fenofibrate group. These data suggest that increased energy dissipation, via hepatic UCP-3 by fenofibrate, contribute to decreased weight gain in obese rats.