Does Adipose Tissue Thermogenesis Play a Role in Metabolic Health?

The function ascribed to brown adipose tissue in humans has long been confined to thermoregulation in neonates, where this thermogenic capacity was thought lost with maturation. Recently, brown adipose tissue depots have been identified in adult humans. The significant oxidative capacity of brown adipocytes and the ability of their mitochondria to respire independently of ATP production, has led to renewed interest in the role that these adipocytes play in human energy metabolism. In our view, there is a need for robust physiological studies determining the relationship between molecular signatures of brown adipose tissue, adipose tissue mitochondrial function, and whole body energy metabolism, in order to elucidate the significance of thermogenic adipose tissue in humans. Until such information is available, the role of thermogenic adipose tissue in human metabolism and the potential that these adipocytes may prevent or treat obesity and metabolic diseases in humans will remain unknown. In this article, we summarize the recent literature pertaining to brown adipose tissue function with the aims of drawing the readers’ attention to the lack of data concerning the role of brown adipocytes in human physiology, and to the potential limitations of current research strategies. 1. Introduction As the combustion engine of respiring cells, the mitochondrion is an essential component of life. Furthermore, as these organelles are principally responsible for the oxidative disposal of glucose and fatty acids, the role of mitochondrial function in the etiology of diseases where substrate metabolism is perturbed has been the focus of a considerable research effort for a number of decades. A notable example of this is the role of mitochondrial capacity in the pathogenesis of skeletal muscle insulin resistance. The reason for such interest in the role of altered skeletal muscle bioenergetics in the development of insulin resistance are several fold; skeletal muscles significant contribution to body mass, the relative abundance of mitochondria within skeletal muscle and their plasticity (particularly in response to muscular contraction), skeletal muscles central role in whole body glucose and fatty acid disposal, and the fact that skeletal muscle can be sampled from humans relatively easily are all contributing factors. With regard to skeletal muscle, whether insulin resistance is indeed the chicken, with mitochondrial dysfunction being the preceding egg, or whether the opposite is the case remains unclear. However, what does seem clear is that measures of skeletal