Metabolic and appetitive regulation of adipocyte mass during treatment of obesity

Adipose mass is homeostatically maintained within a narrow range despite fluctuations in daily calorie intake and activity levels. Constituting an adipose mass "set point," this homeostatic regulation includes sensing mechanisms in the form of hormones reflecting caloric intake that serve as mediators of appetitive behaviors and adipose mass amount; integrating centers in the brain and brainstem; and response or effector systems. During adipose mass fluctuations beyond daily short-term changes, typically during low-calorie dieting, these effector systems include adaptive responses in metabolism (energetics), hormone production, and appetitive behaviors that resist further loss and restore adipose mass to baseline. Although our understanding of the disease of obesity is still evolving, within the context of this paper we consider the disease a manifestation of the pathophysiological processes when the expression of leptin resistance leads to the establishment of a new, higher adipose mass set point. Effective obesity therapies lower the adipose mass set point by improving appetite control and preventing the normal adaptive responses that lead to weight regain, effectively establishing a new adipose mass set point at a lower, healthier level. Conveying this biology to patients with obesity provides them with an understanding of their disease state, why drug and surgical treatments in combination with lifestyle are necessary for most people, and the mediators of the changes in appetitive behaviors expected from effective obesity therapies. Future research will need to advance the evidence base that supports this theoretical framework and generate even deeper insights into the disease of obesity.