Brown Adipose Tissue: A New Human Organ?

Shalini Ojha; Mark Birtwistle; Helen Budge; Michael E Symonds

Disclosures

Expert Rev Endocrinol Metab. 2013;8(2):123-125. 

In This Article

Regulation of BAT

In addition to their presence in discrete BAT depots, brown adipocytes are also found in WAT depots – variously termed as brown-in-white (BRITE) or beige cells. These cells are distinct from classical brown adipocytes[6] and develop from myogenic factor 5 expressing skeletal muscle precursors.[7]

NE stimulation, mediated by β3-adrenergic receptors, is the main activator of BAT,[1] but the detailed mechanisms and pathways involved in BAT development and regulation remain largely undetermined. The meeting provided a number of new insights in this area, such as the role of cholesterol ester transfer protein, which increases lipolysis and enhances β3-adrenergic receptor and UCP1 expression in transgenic mice, increasing energy expenditure and reducing adiposity. Early B-cell factor 2 expressed in myoblasts and white adipocyte precursor cells was reported to recruit the master transcription factor PPARγ and strongly activate transcription of PRDM16, a key regulator of thermogenic genes[7] to brown-specific binding sites, reprogramming precursor cells to a brown adipocyte fate.

Novel studies involving other regulatory mechanisms were also presented. Prolactin-releasing peptide in the dorsomedial hypothalamic nuclei is an important component of the circuitry involved in sympathetic activation of BAT and the lack of its receptor, the G protein-coupled receptor 10, leads to obesity, reduced energy expenditure and shivering to maintain core body temperature despite adequate BAT thermogenic capacity. LR11, a neuronal apolipoprotein receptor implicated in Alzheimer's disease, can negatively regulate thermogenesis in BAT and subcutaneous WAT, but only at thermoneutrality, suggesting a regulatory mechanism independent of adrenergic stimulation. Furthermore, shRNA depletion of pyruvate kinase M2 in white adipocytes promotes the development of a brown-like thermogenic program, and that subcutaneous injection of pyruvate kinase M2-deficient preadipocytes into mice gives rise to ectopic BAT depots. BMP8B is expressed in both BAT and the hypothalamus and was reported to regulate thermogenesis in conjunction with hypothalamic adenosine monophosphate-activated protein kinase.[8]

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