Studies of origins of abnormal sympathetic function in obese Zucker rats

Levin, B. E.; Triscari, J.; Sullivan, A. C.

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.