COLD ACCLIMATION-ASSOCIATED CHANGES IN BROWN ADIPOSE-TISSUE DO NOT NECESSARILY INDICATE AN INCREASE OF NONSHIVERING THERMOGENESIS IN C57BL 6J MICE/

We have reported previously that a cold acclimation procedure (3-hr pa rtial restraint at 6 degrees C, repeated 3 times at 2-week intervals) usually improves the cold tolerance of adult C57BL/6J mice. Those mice that did not improve their cold tolerance had lower cold-induced symp athetic nervous outflow to the interscapular brown adipose tissue (IBA T), suggesting a failure in the mechanisms of nonshivering thermogenes is. To understand the origin of this failure, this study was intended to measure nonshivering thermogenesis in mice that did not improve the ir cold tolerance after the cold acclimation procedure. After being su bjected 3 times to a partial restraint al 6 degrees C, mice were anest hetized with urethane, immobilized with vecuronium bromide, and placed on artificial ventilation. The VO2 and VCO2 in expired air were measu red and metabolic heat production (MHP) was calculated while body temp erature was artificially lowered to 7.5 degrees C below control level. In a separate group of mice, the total amount and concentration of mi tochondrial uncoupling protein, thermogenin (UCP), in IBAT was measure d immediately after completion of the cold-acclimation procedure. The concentration and the amount of UCP in the mitochondria of IBAT was si gnificantly higher in all mice that had been presented to the cold acc limation procedure, regardless of its outcome, than in mice that had n ever been exposed to an environment below room temperature (NAIVE). MH P increased significantly during body cooling in all mice. However, MH P before and during cold stimulation in mice that did not improve thei r cold tolerance as a result of the cold-acclimation procedure was sig nificantly lower than the MHP of animals in which cold tolerance was i mproved, and was not different from MHP of the NAIVE group. Therefore, in mice in which cold tolerance did not improve after repeated cold e xposure, the anatomical and biochemical changes in brown adipose tissu e typical of cold acclimation were not associated with a cold-induced increase in MHP. We infer that the expression of UCP in brown adipose tissue is a necessary, but not sufficient, attribute of cord acclimati on. Cold acclimation, measured as increased cold tolerance, occurs onl y if synthesis of UCP in BAT is associated with an increased cold-indu ced response of the sympathetic nervous system. Copyright (C) 1996 Els evier Science Inc.