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Intestinal lipid–derived signals that sense dietary fat
Nicholas V. DiPatrizio, Daniele Piomelli
Nicholas V. DiPatrizio, Daniele Piomelli
Published February 2, 2015
Citation Information: J Clin Invest. 2015;125(3):891-898. https://doi.org/10.1172/JCI76302.
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Intestinal lipid–derived signals that sense dietary fat

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Abstract

Fat is a vital macronutrient, and its intake is closely monitored by an array of molecular sensors distributed throughout the alimentary canal. In the mouth, dietary fat constituents such as mono- and diunsaturated fatty acids give rise to taste signals that stimulate food intake, in part by enhancing the production of lipid-derived endocannabinoid messengers in the gut. As fat-containing chyme enters the small intestine, it causes the formation of anorexic lipid mediators, such as oleoylethanolamide, which promote satiety. These anatomically and functionally distinct responses may contribute to the homeostatic control and, possibly, the pathological dysregulation of food intake.

Authors

Nicholas V. DiPatrizio, Daniele Piomelli

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Figure 1

Chemical structures and molecular targets of lipid-derived mediators involved in the monitoring of dietary fat.

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Chemical structures and molecular targets of lipid-derived mediators inv...
Left: fatty acyl glycerol esters 2-AG and 2-OG. Right: fatty acyl ethanolamides anandamide (AEA) and OEA. OEA and 2-OG may contribute in complementary ways to the postingestive control of satiety. 2-OG may act as a local regulator of GLP1 release through its ability to activate GPR119 on the apical surface of enteroendocrine L cells of the ileum. It is likely to reach millimolar concentrations in the lumen of the upper gut during fat digestion. OEA is produced by duodenal and jejunal enterocytes and modifies meal patterns in a manner similar to a satiety signal, increasing the time between meals. This activity is dependent on OEA binding of PPARα. OEA also engages GPR119 to drive secretion of GLP1 (27). Anandamide and 2-AG are high-affinity agonists for the GPCR cannabinoid receptors CB1 and CB2. Activation of CB1 increases food intake, enhances reward aspects of eating, and promotes energy conservation (4).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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