Selective increase in cytochrome P450 content in hepatic microsomes from rats with ventromedial hypothalamic lesions

Changes in the components of hepatic microsomal electron transport systems and in drug hydroxylase activities were investigated in ventromedial hypothalamus (VMH) lesioned obese rats. Eight weeks after electrolysis of the bilateral VMH, the content of cytochrome P450 per mg microsomal protein (0.79 +/- 0.07 nmol/mg protein) was significantly higher (P less than 0.02) than that in the sham-operated rats (0.59 +/- 0.02). Cytochrome P450 per whole liver in the VMH-lesioned obese rats had also significantly increased (87 +/- 9 nmol vs 56 +/- 3, P less than 0.02). No significant differences were found in the cytochrome b5 contents, and the activities of NADPH- and NADH-cytochrome c reductases between the VMH-lesioned obese and sham-operated rats. The demethylation activities of aminopyrine (1.04 +/- 0.02 nmol/mg protein/min vs 0.94 +/- 0.02, P less than 0.05) and p-nitroanisole (0.96 +/- 0.02 vs 0.89 +/- 0.02 , p less than 0.02) and the aniline hydroxylase activity (0.22 +/- 0.01 vs 0.16 +/- 0.01, P less than 0.01) were enhanced, but 7-ethoxycoumarin O-deethylase activity was unchanged in the VMH-lesioned obese rats. These results indicate a selective increase in the content of cytochrome P450 among the components of the P450-dependent mixed function oxidase system in the liver of VMH-lesioned obese rats. Our observations suggest that drug metabolism may be enhanced in the hypothalamic obesity.