Adaptive thermogenesis and browning of white adipose tissue in cold acclimated UCP1‐KO mice

Abstract

Uncoupling protein 1 knockout (KO) mice develop hypothermia when acutely exposed to cold. Pre-acclimation to moderate cold (18°C), however, renders these mice cold resistant, suggesting adaptive thermogenesis without functional brown adipose tissue. Previous studies proposed white adipose tissue (WAT) as a contributor to adaptive thermogenesis in KO mice. We measured the recruitment of thermogenic capacity in wildtype (WT) and KO mice after cold acclimation and analyzed the respiratory capacity of WAT. All mice were pre-acclimated to 18°C prior to acclimation at 5°C. Basal metabolic rate and maximal cold-induced heat production (HPmax) of thermoneutral and cold acclimated mice were determined by indirect calorimetry. In thermoneutral controls mean HPmax did not differ between WT and KO (756 and 714 mW, respectively). After cold acclimation HPmax increased to 1230 and 941 mW in WT and KO, respectively. Thus, KO mice exhibit nearly 50% of the adaptive increase observed in WT. In inguinal WAT of KO we measured a 3.6-fold increase of cytochrome c oxidase activity, and a 15-fold increase in the CideA mRNA level, a marker gene for brown adipocytes. Our results strongly suggest enhanced recruitment of brown adipocyte-like cells in WAT of KO mice which may contribute to adaptive thermogenesis in the cold by utilization of a mechanism independent of uncoupling protein 1.