Defective catecholamine metabolism in peripheral organs of genetically obese Zucker rats

Catecholamine (CA) metabolism in peripheral organs of lean and obese, 3-4 and 7-8 month (mo) old male Zucker rats was studied to define further the known abnormalities of peripheral sympatho-adrenal functions in the obese rat. Norepinephrine (NE) levels in all sympathetically innervated organs from obese rats (aorta, heart, pancreas, brown adipose tissue and white adipose tissue) were decreased to 9-55% of those in lean rats at 3-4 mo. NE turnover, measured by inhibition of tyrosine hydroxylase (TH) with a-methyl-p-tyrosine, was also decreased in these same organs. NE levels and turnover were also decreased (by 50-95%) in many, but not all organs assayed of 7-8 mo old obese rats, while there were inconsistent changes in organ dopamine and epinephrine levels at both ages. Decreased NE metabolism was associated with decreased dopamine-beta-hydroxylase (D beta H) activity in every organ assayed from obese rats at 3-4 mo and 7-8 mo of age except in the superior cervical ganglia of 7-8 mo old rats. There were no consistent changes in TH or phenylethanolamine-N-methyltransferase activities. In 3-4 mo old obese rats, decreased D beta H activity was associated with decreased immunoprecipitable enzyme protein in the hearts but not in the adrenal glands, where differences in the affinity for substrate appeared to explain the activity differences. These results suggest that the previously reported defect in stress-induced plasma NE levels in obese rats could be explained by decreased D beta H activity in nerve terminals of their sympathetic nervous system and that, in this case, D beta H may play an important role in the regulation of NE synthesis.