Only a fraction of UCP1 is required to sustain adaptive nonshivering thermogenesis in the cold

Abstract

To address the long-standing question of the respective physiological contributions of classical brown versus beige adipocytes to adaptive nonshivering thermogenesis, we generated mice with lineage-specific ablation of UCP1 in thermogenic adipocytes of myogenic origin. This selectively targeted the major classical brown adipocyte lineage while preserving UCP1 expression in the remaining thermogenic adipocytes, reducing total UCP1 content by approximately 80 %. Unexpectedly, despite this profound reduction in UCP1 abundance, cold acclimation-recruited thermogenic capacity, assessed by adrenergic stimulation, remained largely preserved. In contrast, complete UCP1 deficiency abolished the adrenergically induced thermogenic response, demonstrating that UCP1 is indispensable for adaptive nonshivering thermogenesis. These findings indicate that in cold-acclimated mice only a fraction of the UCP1 normally present is required to sustain maximal thermogenic capacity. We further establish that the capacity to support UCP1-dependent oxidative metabolism, rather than UCP1 abundance, is the principal constraint on maximal thermogenic output under these conditions.