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Impact of Gut and Metabolic Hormones on Feeding Reward

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Ingestion of food activates a cascade of endocrine responses (thereby reflecting a contemporaneous feeding status) that include the release of hormones from the gastrointestinal (GI) tract, such as cholecystokinin (CCK), glucagonlike peptide YY (PYY), peptide PP, and oleoylethanolamide, as well as suppression of ghrelin secretion. The pancreas and adipose tissue, on the other hand, release hormones that serve as a measure of the current metabolic state or the long‐term energy stores, that is, insulin, leptin, and adiponectin. It is well known and intuitively understandable that these hormones target either directly (by crossing the blood‐brain barrier) or indirectly (e.g., via vagal input) the “homeostatic” brainstem‐hypothalamic pathways involved in the regulation of appetite. The current article focuses on yet another target of the metabolic and GI hormones that is critical in inducing changes in food intake, namely, the reward system. We discuss the physiological basis of this functional interaction, its importance in the control of appetite, and the impact that disruption of this crosstalk has on energy intake in select physiological and pathophysiological states. We conclude that metabolic and GI hormones have a capacity to strengthen or weaken a response of the reward system to a given food, and thus, they are fundamental in ensuring that feeding reward is plastic and dependent on the energy status of the organism. © 2021 American Physiological Society. Compr Physiol 11:1425‐1447, 2021.

Figure 1. Figure 1. Summary representation of key gastrointestinal, pancreatic, and adipose hormones that affect activity of the ventral tegmental area (VTA)‐nucleus accumbens (NAcc) pathway, a key circuit in reward processing. Hormones depicted on the green background can cross the blood‐brain barrier, and therefore, they can act directly at the reward sites, whereas the remaining ones affect the brain via the vagal input or central nervous system (CNS) areas where the blood‐brain barrier is weak. CCK, cholecystokinin; GLP‐1, glucagonlike peptide‐1; OEA, oleoylethanolamide.

Figure 1. Summary representation of key gastrointestinal, pancreatic, and adipose hormones that affect activity of the ventral tegmental area (VTA)‐nucleus accumbens (NAcc) pathway, a key circuit in reward processing. Hormones depicted on the green background can cross the blood‐brain barrier, and therefore, they can act directly at the reward sites, whereas the remaining ones affect the brain via the vagal input or central nervous system (CNS) areas where the blood‐brain barrier is weak. CCK, cholecystokinin; GLP‐1, glucagonlike peptide‐1; OEA, oleoylethanolamide.
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Anica Klockars, Allen S. Levine, Mitchell A. Head, Claudio E. Perez‐Leighton, Catherine M. Kotz, Pawel K. Olszewski. Impact of Gut and Metabolic Hormones on Feeding Reward. Compr Physiol 2021, 11: 1425-1447. doi: 10.1002/cphy.c190042