Pathophysiology of Obesity

The pathogenesis of obesity is complex and still not completely understood. It involves a multifaceted system of hormones, peptides, and adipokines and their intersection with the environment as well as genetics.

At its core, obesity results when the amount of energy in one’s food intake is greater than the amount of energy expended. Unfortunately, for too long that’s meant viewing obesity as a condition someone can manage on their own simply by eating less and moving more. It’s definitely not that simple.

Energy balance begins in the brain, with the hypothalamus continually working towards homeostasis between appetite and satiety. A complex symphony of hormones and peptides from the digestive tract (ghrelin, PYY, CCK, leptin), the pancreas (insulin), and adipose tissue (leptin) directly converge upon the arcuate nucleus in the hypothalamus or send messages via the intermediate of afferent neurons of the vagus nerve (which carry receptors for PYY, CKK, leptin and ghrelin) (Table 1). Collectively they provide a symbolic representation of the feeding status. These messages are then translated into either a food-seeking (orexic) or a fasting (anorexic) behavior.³ Figure 1 illustrates the complexity of the food regulation system.