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Gastrointestinal regulation of food intake
David E. Cummings, Joost Overduin
David E. Cummings, Joost Overduin
Published January 2, 2007
Citation Information: J Clin Invest. 2007;117(1):13-23. https://doi.org/10.1172/JCI30227.
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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 2

Topography of enteroendocrine cells and absorptive enterocytes on a villus within the small-intestinal wall.

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Topography of enteroendocrine cells and absorptive enterocytes on a vill...
Enteroendocrine cells sense nutritive and non-nutritive properties of luminal food and, in response, release satiation peptides from their basolateral aspect. These signals diffuse through the lamina propria to activate nearby vagal- and spinal-afferent fibers from neurons within the nodose and dorsal root ganglia, respectively, as well as myenteric neurons. Satiation peptides can also enter the bloodstream to act distantly as hormones. Gut-peptide release is regulated not only by luminal nutrients but also by somatic signals. The basolateral side of enteroendocrine cells bears receptors that respond to neurotransmitters, growth factors, and cytokines. Neurotransmitters mediate duodenal-ileal communication to regulate L cell secretion, and they enable central modulation of gut-peptide release. Whether vagal- or spinal-afferent nerves are directly activated by ingested nutrients is uncertain. Although vagal- and spinal-afferent fibers approach the abluminal aspect of enteroendocrine cells and enterocytes, they do not form synapse-like contacts with these epithelial cells, nor do they extend to the intestinal lumen. Some subepithelial nerve fibers might respond to luminal chemicals that diffuse across the epithelium, such as FAs, but this applies only to short-chain FAs, which do not efficiently elicit satiation (116). Other vagal-afferent fibers respond selectively to intestinal carbohydrates or fats. Although it is theoretically possible that these neurons sense nutrients in the extracellular space, it is more clearly established that signaling molecules released from enteroendocrine cells mediate macronutrient-specific neural activation.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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