Metabolic regulation and the anti-obesity perspectives of human brown fat

Abstract

Activation of brown adipose tissue (BAT) in adult humans increase glucose and fatty acid clearance as well as resting metabolic rate, whereas a prolonged elevation of BAT activity improves insulin sensitivity. However, substantial reductions in body weight following BAT activation has not yet been shown in humans. This observation raise the possibility for feedback mechanisms in adult humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines, factors produced by and secreted from brown fat. Batokines also seems to be involved in BAT recruitment by stimulating proliferation and differentiation of brown fat progenitors. Increasing human BAT capacity could thus include inducing brown fat biogenesis as well as identifying novel batokines. Another attractive approach would be to induce a brown fat phenotype, the so-called brite or beige fat, within the white fat depots. In adult humans, white fat tissue transformation into beige has been observed in patients with pheochromocytoma, a norepinephrine-producing tumor. Interestingly, human beige fat is predominantly induced in regions that were BAT during early childhood, possibly reflecting that a presence of human beige progenitors is depot specific and originating from BAT. In conclusion, to utilize the anti-obesity potential of human BAT focus should be directed towards identifying novel regulators of brown and beige fat progenitor cells, as well as feedback mechanisms of BAT activation. This would allow for identification of novel anti-obesity targets.