Molecular evolution of thermogenic uncoupling protein 1 and implications for medical intervention of human disease

In eutherian mammals, brown adipose tissue (BAT) permits non-shivering thermogenesis (NST) through high metabolic rates catalyzed by the unique mitochondrial uncoupling protein 1 (UCP1). The tissue has recently gained remarkable attention due to its discovery in adult humans. Approaching BAT and UCP1 as therapeutic targets to combust surplus energy bares high potential to combat the epidemic of the metabolic syndrome that has precipitated in our society as a result of our modern lifestyles. Our understanding of the physiological and molecular control of BAT may benefit tremendously from consideration of its evolution that basically outlines the blueprint of how to construct a fat burning tissue. Here, we discuss the evolutionary history of UCP1 and BAT, from its origins and emergence to its downfall in several mammalian lineages. Additionally, we delineate the annotation of UCPs in vertebrates by analyzing genomic organization and summarize the phylogeny of UCP1 within the closest relatives of humans, the great apes. Outlining whether the molecular networks controlling thermogenesis in adipose tissue (commonly known as the "browning potential") pre-dated the classical thermogenic function of BAT and UCP1, and whether the evolutionary inactivation of UCP1 enhanced compensatory thermogenic mechanisms, should be of major interest to those who aim to access adipose tissue thermogenesis in a biomedical context.