Peripheral Modulators of Appetite in Eating Disorders

Regulation of food intake is complex, with many peripheral and central inputs. The goal of these inputs is homeostatic maintenance of stable weight and optimal nutrient supplies. Homeostatic regulation includes central mechanisms in the hypothalamus and peripheral short- and long-term mechanisms, mediated mainly by gastrointestinal and adipose tissue peptides. Appetite and feeding regulating factors can be described as orexigenic (appetite and feeding-enhancing) or anorexigenic (appetite and feeding-reducing). Orexigenic factors involve peripheral ghrelin and the centrally acting NPY/AgRP system. Anorexigenic factors include gastrointestinal peptides, the adipose tissue hormone leptin, and the centrally acting melanocortin system. In addition to homeostatic regulation, hedonic and cognitive feedback neurocircuits influence feeding and appetite, and their dysfunction plays an essential role in the onset and maintenance of several psychiatric diseases, mainly eating disorders. In-depth knowledge of changes in brain connectivity and central and peripheral mechanisms of food intake regulation is crucial for understanding the pathogenesis of eating disorders, obesity, and comorbidities.