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*

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Abstract
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.