Endothermy depends on the ability to generate heat beyond basal metabolic output. The transition from incidental metabolic heat production to regulated adaptive thermogenesis represents a critical, yet poorly understood milestone in vertebrate evolution. In vertebrates, adaptive thermogenesis includes shivering thermogenesis and non-shivering thermogenesis (NST), the latter involving molecular mechanisms that release energy in the form of heat independently of muscle contraction. This review synthesizes physiological, comparative, and evolutionary findings on adaptive NST, with a focus on adipose-based thermogenesis mediated by its unique mitochondrial uncoupling protein 1 (UCP1). We highlight a two-stage evolutionary model in which a pre-thermogenic adipose program governing UCP1 expression preceded the emergence of efficient UCP1-mediated thermogenesis in eutherian mammals. The source of NST and underlying mechanisms in other tissues and in non-eutherian endothermic vertebrates are less well understood. We discuss proposed UCP1-independent sources of cellular heat production in adipose tissue and muscle. Although these pathways can increase cellular energy expenditure, evidence supporting their role as dedicated and regulated thermogenic mechanisms remains limited to date. Collectively, these findings suggest that adaptive NST is not a singular conserved mechanism but a diverse and context dependent evolutionary strategy with important implications for understanding human physiology and disease.
Keuper et al. (Mon,) studied this question.