Regulation of adipocyte thermogenesis: mechanisms controlling obesity

Adipocyte biology has been intensely researched in recent years due to the emergence of obesity as a serious global health concern and because of the realization that adipose tissue is more than simply a cell type that stores and releases lipids. The plasticity of adipose tissues, to rapidly adapt to altered physiological states of energy demand, is under neuronal and endocrine control. The capacity for white adipocytes to store chemical energy in lipid droplets is key for protecting other organs from the toxic effects of ectopic lipid deposition. In contrast, thermogenic (brown and beige) adipocytes combust macronutrients to generate heat. The thermogenic activity of adipocytes allows them to protect themselves and other tissues from lipid overaccumulation. Advances in brown fat biology have uncovered key molecular players involved in adipocyte determination, differentiation, and thermogenic activation. It is now, well appreciated that three distinct adipocyte types exist: white, beige, and brown. Moreover, functional differences are present within adipocyte subtypes located in anatomically distinct locations. Adding to this complexity is the recent realization from single-cell sequencing studies that adipocyte progenitors are also heterogeneous. Understanding the molecular details of how to increase the number of thermogenic fat cells and their activation may delineate some of the pathophysiological basis of obesity and obesity-related diseases. Here, we review recent advances that have extended our understanding of the central role that adipose tissue plays in energy balance and the mechanisms that control their amount and function.