Studies of origins of abnormal sympathetic function in obese Zucker rats

To explain previously described abnormalities of sympathetic function in the genetically obese Zucker rat, the kinetics of norepinephrine (NE) metabolism were examined. Lower stress-induced levels of plasma NE in the obese rat were shown to be due to decreased release of NE because uptake of [3H]NE tracer from plasma was 45% slower in the obese compared with the lean rat. NE levels were 15, 20, and 34% lower in heart, pancreas, and interscapular brown adipose tissue (IBAT), and NE turnover rates (determined by two independent methods) were 39-48 and 43-69% lower in the pancreas and IBAT of obese compared with lean rats. In vivo synthesis of [3H]NE from [3H]dopamine by the enzyme dopamine beta-hydroxylase was 60% lower in IBAT but was equal in hearts of obese compared with lean rats. These results suggest an organ-specific decrease of NE synthesis in the obese Zucker rat, possibly due to decreased dopamine beta-hydroxylase activity in IBAT.