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Gastrointestinal regulation of food intake
David E. Cummings, Joost Overduin
David E. Cummings, Joost Overduin
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Review Series

Gastrointestinal regulation of food intake

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Abstract

Despite substantial fluctuations in daily food intake, animals maintain a remarkably stable body weight, because overall caloric ingestion and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. The brain receives hormonal, neural, and metabolic signals pertaining to body-energy status and, in response to these inputs, coordinates adaptive alterations of energy intake and expenditure. To regulate food consumption, the brain must modulate appetite, and the core of appetite regulation lies in the gut-brain axis. This Review summarizes current knowledge regarding the neuroendocrine regulation of food intake by the gastrointestinal system, focusing on gastric distention, intestinal and pancreatic satiation peptides, and the orexigenic gastric hormone ghrelin. We highlight mechanisms governing nutrient sensing and peptide secretion by enteroendocrine cells, including novel taste-like pathways. The increasingly nuanced understanding of the mechanisms mediating gut-peptide regulation and action provides promising targets for new strategies to combat obesity and diabetes.

Authors

David E. Cummings, Joost Overduin

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Figure 4

Central and peripheral sites at which the long-acting adiposity hormone leptin potentiates the actions of short-acting GI satiation factors.

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Central and peripheral sites at which the long-acting adiposity hormone ...
Leptin-receptor signaling within the hypothalamus indirectly augments hindbrain neuronal responses to gut satiation signals, such as CCK, through hypothalamus-hindbrain projections involving oxytocin and other neuropeptides (10, 11). Central responses to CCK are also augmented by leptin acting directly on the hindbrain. In the periphery, leptin potentiates GI satiation signals both by enhancing gut-peptide secretion (for example, GLP1 release from distal-intestinal L cells) and by heightening vagal-afferent responsiveness to gut peptides (for example, to CCK from proximal-intestinal I cells). LepR, leptin receptor.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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