Molecular aspects of medicine
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Endothermy requires a source of endogenous heat production. In birds, this is derived primarily from shivering, but in mammals it is mostly non-shivering thermogenesis (NST). Brown adipose tissue (BAT) is a specialized tissue found in Eutherian mammals that is the source of most NST. ⋯ Additional regulatory factors include bone morphogenic proteins, fibroblast growth factor 21, Vascular endothelial growth factors and transient receptor potential vanilloid receptors which are important components of thermal sensing and hence how brown adipose tissue responds to the cold. In the future the main challenge is to understand how these regulatory factors combine with each other and with inhibitory factors to control heat production from BAT, and what their relative importance is in differing circumstances. Knocking out UCP1 has revealed other sources of heat production in BAT including creatine-dependent cycles and a futile cycle of Ca2+ shuttling into and out of the endoplasmic reticulum via the SERCA and ryanodine receptors.