When brown fat sparked fire

Brown adipose tissue (BAT) is the main heater organ in hibernators, newborns, and small mammals that permits adaptive non-shivering thermogenesis (NST) in cold environments [1].To produce heat, a key mitochondrial protein, called uncoupling protein 1 (UCP1), increases mitochondrial proton leak, leading to futile proton cycling via the electron transport chain that ratchets up mitochondrial heat production (Figure 1).The evolutionary origin of the heat producing mechanism of this unique mammalian tissue was unknown until recently.Our research team discovered that UCP1 gained its thermogenic ability in the stem ancestor of placental (eutherian) mammals to ignite BAT [3].Contrasting previous assumptions that BAT is "found in all mammals" or a "mammalian prerogative" to survive cold stress (e.g.1), the onset of BAT thermogenesis can now be considered rather late during mammalian evolution, after marsupials diverged from the placental lineage (~150 million years ago).Our study shows that the adipose tissue of the gray short-tailed opossum, Monodelphis domestica, a marsupial species, displays only a partial transcriptomic signature that is usually found in BAT of placentals [3].Strikingly, the marsupial variant of UCP1 does not show its typical thermogenic activity by uncoupling mitochondrial respiration.To exclude that thermogenic functionality has been lost specifically in the marsupial lineage, a comprehensive phylogeny of UCP1 was built on a wealth of genomic data of more than 200 species, allowing ancestral UCP1 sequence reconstructions with high confidence.Functional assays demonstrate that the reconstructed stem eutherian UCP1 produces heat, contrasting with the nonthermogenic stem therian variant (therian = before marsupials and placentals diverged; Figure 1).Collectively, these studies conclusively demonstrate that UCP1 sparked fire only in the placental lineage [3].The thermogenic mechanisms by which some animals are able to defend high body temperatures during cold challenges have captivated researchers for ages.In many vertebrates including endothermic fish (e.g.some tuna and shark species), heat generation is increased by muscle activity, while in endothermic birds and mammals, inefficient mitochondrial energy conversion is supported by a high basal mitochondrial proton leak, representing a hallmark that permits high basal metabolic rates and body temperatures [4].However, adaptive thermogenic mechanisms require an array of regulatory steps to allow the animal to adjust heat output to changing environmental temperatures.Two forms of adaptive thermogenesis are known: shivering thermogenesis by involuntary, periodic muscle contractions, and NST, the ability to engage molecular mechanisms increasing cellular chemical heat release without muscular contraction.Shivering is an immediate response to cold but hampers motility and activity, contrasting adaptive NST which enables prolonged adaptation to cold, replacing shivering in the long term.Since both birds and mammals possess muscles with high oxidative power, some researchers have searched for the existence of muscle-based NST mechanisms (reviewed by 5) as an ancient, shared form of thermogenesis in amniotes.However, the underlying molecular mechanisms are debated, and it is unknown how muscle-based NST is regulated, coordinated with muscular contraction, and how much heat is actually produced [5].