Effects of LY104119, a thermogenic weight-reducing compound, on norepinephrine concentrations and turnover in obese and lean mice

Abstract

Dopamine (DA) accumulation in interscapular brown adipose tissue (IBAT), heart, and liver was linear for more than 60 min after injection of 1-cyclohexyl-2-mercapto-imidazole (CHMI), a DA beta-hydroxylase inhibitor, into mice and served as an index of the rate of synthesis of norepinephrine (NE) in these tissues. There was a marked diurnal rhythm of DA accumulation in all three tissues of mice fed ad libitum, the rhythm being dampened in obese mice in IBAT and liver but not in heart. LY104119 acutely decreased NE concentration in IBAT, heart and liver, but not in brain, and it also decreased DA accumulation after CHMI in IBAT, heart and liver. Chronic administration of LY104119 at doses that stimulated thermogenesis and reduced body weight decreased NE turnover in heart and liver but increased NE turnover in IBAT. These data suggest that the increased thermogenesis in IBAT after chronic LY104119 treatment may be mediated by increased noradrenergic tone.