Effects of a peroxisome proliferator on beta-oxidation and overall energy balance in obese (fa/fa) rats.

The aim of the study was to examine in the obese Zucker (fa/fa) rats the effect of a peroxisome proliferator nafenopin on liver and brown adipose tissue peroxisomal and mitochondrial beta-oxidation enzyme activities and on the overall energy dissipation. A 17-day nafenopin treatment increased liver wet weight 2.1-fold and liver total acyl-CoA oxidase and mitochondria beta-oxidative activities 32- and 4.6-fold, respectively. It increased the interscapular brown adipose tissue (IBAT) acyl-CoA oxidase activity 2.1-fold but had no effect on the mitochondria beta-oxidative activity. Because nafenopin was found to decrease food intake by 22%, obese nafenopin-treated rats were compared with a group of obese pair-fed rats. Both food restriction and nafenopin treatment decreased body weight gain, but a decrease (14%) in fat content was only observed in nafenopin-treated rats. Food restriction of obese rats decreased the mean metabolic rate by 13%, and nafenopin treatment prevented this decrease. Both food restriction and nafenopin treatment decreased the mean daily respiratory quotient (RQ). However, the RQ of nafenopin-treated rats was steadily lower than that of control, whereas that of food-restricted rats was the same as that of control animals during the feeding period and decreased when food supply was exhausted. The increase in liver and IBAT fatty acid beta-oxidative activities may be the cause of the decreased lipid accretion measured in obese rats.