The Physiology of Thermogenesis: acute and adaptive processes in brown adipose tissue

Thermogenesis is the use of energy with the purpose of only producing heat, a wasteful process that Nature would normally avoid. Nonetheless, through developing the unique process of nonshivering thermogenesis, mammals gained in evolutionary terms. Nonshivering thermogenesis emanates from the activity of the mitochondrial protein UCP1 in brown adipose tissue.

In this project, we will use novel model systems to advance the understanding of mammalian thermogenesis, at three levels of organization:- At the organism level, through new mouse models, we will establish the relative significance of two adipose tissues, brown and brite/beige, for both classical cold-induced nonshivering thermogenesis and for diet-induced thermogenesis – the latter a process that, due to its potential significance for energy balance, has gained much interest.- At the cellular level, from new transcriptome data sets, we will identify novel molecular actors regulating brown adipocyte differentiation.- At the molecular level, through a newly developed flexible model of ectopically expressed UCP1, we will characterize regulation of the activity of UCP1 in a mitochondrial environment, and identify important structural features in UCP1.The studies have broad interest in that brown adipose tissue, in addition to being important for survival of small mammals (including human newborns) exposed to cold, is now known to be active in a significant fraction of adult humans and may thus affect human energy balance.