Endocrine Abstracts

Brown adipocytes in dedicated depots of brown adipose tissue (BAT) arise from cellular precursors that also give rise to skeletal muscle cells. We found that early B cell factor-2 (Ebf2) expression in the mesoderm of mouse embryos marks brown fat precursors that are destined to activate Pparγ expression and differentiate into Ucp1+ brown adipocytes. Loss of Ebf2 in mice causes a very severe defect in BAT development and function. Ebf2 cooperates with Pparγ to activate expression of many brown fat-selective target genes, including Prdm16, a key transcriptional co-activator in brown adipocytes. Surprisingly, genetic loss of Prdm16 specifically in the brown fat lineage does not disrupt embryonic BAT formation or the expression of brown fat-specific genes. Interestingly however, Prdm16-deficiency caused ectopic expression of white fat-selective genes and a severe aging-associated decline in the thermogenic characteristics of BAT. Prdm16-deficient BAT from older mice had reduced mitochondrial content and function. Moreover, animals lacking Prdm16 in BAT had a severely depressed capacity to increase their energy expenditure in response to β-adrenergic activators or cold. Importantly, BAT-selective deletion of Prdm16 impaired BAT function but did not affect the thermogenic ‘beige’ adipocyte population in WAT; this serves as a model to distinguish the effects of brown and beige adipocytes in systemic metabolism.