The gut-brain axis in appetite, satiety, food intake, and eating behavior: Insights from animal models and human studies

Abstract

The gut-brain axis plays a pivotal role in the finely tuned orchestration of food intake, where both homeostatic and hedonic processes collaboratively control our dietary decisions. This interplay involves the transmission of mechanical and chemical signals from the gastrointestinal tract to the appetite centers in the brain, conveying information on meal arrival, quantity, and chemical composition. These signals are processed in the brain eventually leading to the sensation of satiety and the termination of a meal. However, the regulation of food intake and appetite extends beyond the realms of pure physiological need. Hedonic mechanisms, including sensory perception (i.e., through sight, smell, and taste), habitual behaviors, and psychological factors, exert profound influences on food intake. Drawing from studies in animal models and human research, this comprehensive review summarizes the physiological mechanisms that underlie the gut-brain axis and its interplay with the reward network in the regulation of appetite and satiety. The recent advancements in neuroimaging techniques, with a focus on human studies that enable investigation of the neural mechanisms underpinning appetite regulation are discussed. Furthermore, this review explores therapeutic/pharmacological strategies that hold the potential for controlling food intake.

Keywords: GLP‐1; brain imaging; fMRI; gut–brain axis; hedonic; homesostatic; obesity.

FIGURE 1

Schematic of the central neural circuitry in reward, motivation, and food intake. Peripheral neural and hormonal signals are integrated in the hindbrain and hypothalamus. These signals are relayed through the thalamus and midbrain and integrated with corticolimbic signals in the striatum. Projections from the striatum to the pallidum and hypothalamus enable coordination of motivated behavioral responses and reward seeking behavior. Hedonic “hotspots” are shown in red. AP, area postrema; ARC, arcuate nucleus; BNST, bed nucleus of the stria terminalis; DMH, dorsal medial hypothalamus, LHA, lateral hypothalamic area; MDT, mediodorsal thalamic nucleus; NAc, nucleus accumbens; NTS, nucleus of the solitary tract; PBN, parabrachial nucleus; PVH, paraventricular hypothalamus; PVT, paraventricular thalamic nucleus; SNc, substantia nigra pars compacta; VMH, ventromedial hypothalamus; VTA, ventral tegmental area. Created with BioRender.com.

FIGURE 2

Potential mechanisms of weight loss caused by the effects of GLP‐1 and its analogues on the 7 transmembrane domain GLP‐1R along the gut–brain axis. The red arrowhead indicates a decrease and the green arrowhead indicates an increase. GI, gastrointestinal; GLP‐1, glucagon‐like peptide 1; GLP‐1R, glucagon‐like peptide 1 receptor. Created with BioRender.com.