Homeostatic regulation of food intake

Abstract

Food intake and energy expenditure are key regulators of body weight. To regulate food intake, the brain must integrate physiological signals and hedonic cues. The brain plays an essential role in modulating the appropriate responses to the continuous update of the body energy-status by the peripheral signals and the neuronal pathways that generate the gut-brain axis. This regulation encompasses various steps involved in food consumption, include satiation, satiety, and hunger. It is important to have a comprehensive understanding of the mechanisms that regulate food consumption as well as to standardize the vocabulary for the steps involved. This review discusses the current knowledge of the regulation and the contribution peripheral and central signals at each step of the cycle to control appetite. We also highlight how food intake has been measured. The increasingly complex understanding of regulation and action mechanisms intervening in the gut-brain axis offers ambitious targets for new strategies to control appetite.

Keywords: Food intake; Hunger; Satiation; Satiety.

Figure 1.

Food intake cycle. Satiation determines meal termination, while satiety fading and hunger increasing lead to food consumption.

Figure 2.

Peripheral signals for satiation. Gastric accommodation keeps a normal stretch perception until mechanoreceptors perceive gastric distention, and the vagus nerve transmits the signal to the nucleus of the solitary tract. Cholecystokinin also reaches the central nervous system by circulation.

Figure 3.

Peripheral signals for satiety. The vagus nerve regulates gastric emptying through the inhibitory and excitatory vagal circuits. CCK and GLP-1 modulate GE as well by the process known as the ileal brake. Leptin, PYY, and GLP-1 regulate the central activation by endocrine regulation and stimulation through the vagus nerve.

Figure 4.

Central regulation of food intake. Satiation and satiety signals originated in the periphery stimulate the pro-opiomelanocortin and the cocaine- and amphetamine-related transcript (POMC/CART) neurons in the arcuate nucleus of the hypothalamus. These neurons release aMSH, which activates the melanocortin receptor 4 (MC4R) in the paraventricular nucleus (PVN). The PVN relays the signal to the brainstem, cortex and basal ganglia to stop food intake. Satiation and satiety also inhibit the Agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus. The activation of AgRP neurons results in GABA and neuropeptide Y (NPY) release. The release of GABA and NPY inhibit the MC4R, resulting in meal initiation.