Alterations of brown adipose tissue in genetically obese (ob/ob) mice. I. Demonstration of loss of metabolic response to nerve stimulation and catecholamines and its partial recovery after fasting or cold adaptation.

Metabolic responses to electrical nerve stimulation or norepinephrine of isolated interscapular brown adipose tissue (BAT) from lean and ob/ob mice were studied using either continuous monitoring of the NAD(P)H/NAD(P) redox state or direct microcalorimetry. The responses to these sympathetic stimuli were not significantly different from zero in BAT of ob/ob mice kept at 22 C and fed ad libitum. The metabolic rate of BAT of lean mice was stimulated 3-fold by norepinephrine. ob/ob mice are hyperglycemic and hyperinsulinemic; cold adaptation further increased their plasma glucose, and fasting decreased the levels of both glucose and insulin to normal values. Both fasting and cold adaptation at 5 C partially restored the tissue metabolic response of ob/ob mice, whereas a decreased sensitivity was observed in the tissue of lean mice. The results of these experiments are compatible with the hypothesis that the impaired capacity of BAT of ob/ob mice to produce heat could be one of the causes of their high food efficiency and their inability to withstand acute cold exposure.