POTENTIAL DEFECT IN THE VASCULAR CONTROL OF NONSHIVERING THERMOGENESIS IN THE OBESE ZUCKER RAT HIND-LIMB

Vascular control of nonshivering thermogenesis in the perfused hind li mb of obese and lean Zucker rats was compared using two vasoconstricto rs, norepinephrine and serotonin. For hind limbs of both phenotypes, n orepinephrine infusions resulted in a dose-dependent uninterrupted inc rease in perfusion pressure and a biphasic change in oxygen uptake (VO 2), characterized by a stimulation at low concentrations, and an incre asing inhibition at higher concentrations that gradually overcame the stimulation in a dose-dependent manner. At concentrations of norepinep hrine greater than 1 mu M, the inhibitory effect predominated and gave rise to values for VO2, less than basal. The obese hind limb had a lo wer basal VO2 and a lower maximal VO2, mediated by norepinephrine than the lean rat, but these differences appeared to relate largely to the lower muscle mass and higher content of fat of the obese hind limb. S erotonin infusions resulted in a dose-dependent increase in perfusion pressure and an accompanying decrease in VO2. Pressure changes were id entical for the obese and lean hind limbs, but the decrease in VO2 due to serotonin was greater in the hind limbs from the lean rats, and th is difference remained when the data were expressed in terms of muscle mass perfused. It is concluded that the relatively lower content of m uscle of the obese hind limb accounts for its lower basal and lower ma ximal norepinephrine-mediated thermogenesis. In addition, an intrinsic defect in obese hind limb muscle response to serotonin is present, wh ich may be indicative of a decrease in the potential for vasoconstrict or-regulated thermogenesis that could have implications for whole-body energy balance by the obese phenotype.