ABSTRACT

The regulation of energy homeostasis occurs via a complex bidirectional communication network between the brain and the periphery, particularly adipose tissue. The most effective approach for the treatment of obesity would be to target both sides of the energy balance equation: food intake and energy expenditure. Adipose tissue is a highly complex, heterogeneous organ that plays a key role not only in the storage and oxidation of excess calories but also in informing the brain of the systemic energy status. White adipocytes are the primary cells of energy storage and serve to protect the body from ectopic lipid accumulation, whereas brown adipocytes function to waste excess energy as heat. Impaired white adipose tissue health leads to weight gain and metabolic dysfunction. Thus, improving the metabolic activity of the adipocyte protects from obesity and its associated comorbidities. Further, fat cells release an array of signaling factors that may also be therapeutically leveraged for the treatment of excess adiposity. Examples include leptin, a suppressor of appetite, FGF21 as a cold-induced factor that targets multiple organs to increase whole-body thermogenesis, and adiponectin, which influences insulin sensitivity at multiple levels. Hence, combining the actions of these adipocyte-derived factors may offer a novel approach for the management of obesity and maintenance of insulin sensitivity, and as such, places adipose tissue center stage as a target for intervention.