The genetics of brown adipose tissue.

Brown adipose tissue is highly differentiated and has evolved as a mechanism for heat production based upon uncoupling of mitochondrial oxidative phosphorylation. Additionally, large amounts of lipid can be stored in the cells to provide fuel necessary for heat production upon adrenergic stimulation from the central nervous system, and a highly developed vascular system evolved to rapidly deliver heat to vital organs. For unknown reasons, the development of brown adipocytes has two independent pathways: one originates from muscle progenitor cells in the fetus and leads to a fully functional cell at birth (interscapular-type brown fat), while the other transiently emerges in traditional white fat depots at weaning, regresses, and then can be induced in adult mice upon adrenergic stimulation. No genetic variants have been found for interscapular fat, but naturally occurring alleles at eight genetic loci in mice lead to over 100-fold variation for brown adipocytes in white fat upon adrenergic stimulation. The ability to activate this potential for energy expenditure is of great interest in obesity research.