Human brown fat and metabolic disease: a heated debate

Mammals maintain thermoregulation in the face of cold environmental temperatures by activating bioenergetic mechanisms that increase heat production. Included in this response is both shivering (rapid contraction and relaxation of skeletal muscles) and nonshivering thermogenesis. Nonshivering thermogenesis involves the activation of energyexpending brown adipose tissue (BAT), a mitochondria-rich fat tissue that utilizes multiple futile energy-cycling mechanisms to produce heat. Moreover, in response to cold, white adipose tissue (WAT) undergoes a pronounced thermogenic remodeling in which this energy-storing fat tissue adopts a BAT-like phenotype with the emergence of thermogenic fat cells called beige adipocytes. From both a basic science and translational perspective, the study of adipose thermogenesis and its relationship to systemic energy balance remains of great interest. The thermogenic response of adipose tissue exemplifies the remarkable plasticity of this tissue at multiple levels. The study of adipose thermogenesis offers a lens through which several aspects of mitochondrial function, nutrient oxidation, cell differentiation, and tissue remodeling can be explored. The potential for adipocyte thermogenesis to increase metabolic rate makes brown fat cells, in principle, an attractive therapeutic target to treat obesity and cardiometabolic diseases. 2008 to 2009 marked a turning point In 2008, Seale, et al. reported the surprising finding that murine brown adipocytes emerging during development emanate from Myf5+ cells of the skeletal muscle lineage (1). The idea that brown [...]