Molecular mechanisms of appetite regulation

Abstract

The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic β-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation.

Keywords: Adiposity; Appetite; Hypothalamus; Leptin; Satiety.

Fig. 1

Hypothalamic nuclei involved in appetite regulation. ARC, arcuate nucleus; AM, amygdala; CC, corpus callosum; CCX, cerebral cortex; DMN, dorsomedial nucleus; FX, fornix; HI, hippocampus; LHA, lateral hypothalamic area; ME, median eminence; OC, optic chiasm; PFA, perifornical area; PVN, paraventricular nucleus; SE, septum; 3V, third ventricle; TH, thalamus; VMN, ventromedial nucleus.

Fig. 2

A schematic representation of the multiple systems regulating appetite. AgRP, agouti-related peptide; ARC, arcuate nucleus; CCK, cholecystokinin; GLP-1, glucagon-like peptide 1; LHA, lateral hypothalamic area; NPY, neuropeptide Y; NTS, nucleus of the solitary tract; OXM, oxyntomodulin; POMC, pro-opiomelanocortin; PP, pancreatic polypeptide; PVN, paraventricular nucleus; PYY, peptide YY.