Dietary fat sensing via fatty acid oxidation in enterocytes: possible role in the control of eating

Abstract

Various mechanisms detect the presence of dietary triacylglycerols (TAG) in the digestive tract and link TAG ingestion to the regulation of energy homeostasis. We here propose a novel sensing mechanism with the potential to encode dietary TAG-derived energy by translating enterocyte fatty acid oxidation (FAO) into vagal afferent signals controlling eating. Peripheral FAO has long been implicated in the control of eating (141). The prevailing view was that mercaptoacetate (MA) and other FAO inhibitors stimulate eating by modulating vagal afferent signaling from the liver. This concept has been challenged because hepatic parenchymal vagal afferent innervation is scarce and because experimentally induced changes in hepatic FAO often fail to affect eating. Nevertheless, intraperitoneally administered MA acts in the abdomen to stimulate eating because this effect was blocked by subdiaphragmatic vagal deafferentation (21), a surgical technique that eliminates all vagal afferents from the upper gut. These and other data support a role of the small intestine rather than the liver as a FAO sensor that can influence eating. After intrajejunal infusions, MA also stimulated eating in rats through vagal afferent signaling, and after infusion into the superior mesenteric artery, MA increased the activity of celiac vagal afferent fibers originating in the proximal small intestine. Also, pharmacological interference with TAG synthesis targeting the small intestine induced a metabolic profile indicative of increased FAO and inhibited eating in rats on a high-fat diet but not on chow. Finally, cell culture studies indicate that enterocytes oxidize fatty acids, which can be modified pharmacologically. Thus enterocytes may sense dietary TAG-derived fatty acids via FAO and influence eating through changes in intestinal vagal afferent activity. Further studies are necessary to identify the link between enterocyte FAO and vagal afferents and to examine the specificity and potential physiological relevance of such a mechanism.

Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats

“…The increased expression of ketogenesis enzymes in enterocytes rather than hepatocytes in vivo and the stimulation of FAO in enterocyte models in vitro are consistent with this metabolic shift and suggest it occurred primarily in enterocytes. Together with other results implicating peripheral, but not hepatic, FAO in the control of eating ( 18 ), these fi ndings support the hypothesis that an increase in enterocyte FAO due to DGAT-1 inhibition contributes to the observed food intake reduction.…”

“…In addition, we measured the effect of DGAT-1i on fatty acid oxidation (FAO) in intestinal epithelial cell culture models. A stimulatory effect of DGAT-1 inhibition on enterocyte FAO together with a reduction in food intake would be interesting because peripheral, in particular enterocyte, FAO has been implicated in the control of eating ( 18 ).…”

Short-term feed intake is regulated by macronutrient oxidation in lactating Holstein cows

“…In addition to these humoral signals, metabolic oxidation in peripheral organs, specifically fatty acid oxidation in the liver, intestine, and muscle (Scharrer and Langhans, 1986;Friedman et al, 1999;Langhans et al, 2011) and carbohydrate oxidation, primarily he-patic and muscular glycolysis (Friedman and Tordoff, 1986), signal through the autonomous nervous system to the brain for terminating feed intake. In contrast, inhibition of peripheral fatty acid and carbohydrate oxidation increases feed intake (Friedman et al, 1999;Del Prete et al, 2004).…”

Control of food intake by metabolism of fuels: a comparison across species

“…Although intrajejunal infusion of MA stimulated feeding, the site of administration might have minimised response from vagal afferents and cholecystokinin release in the duodenum and the feeding response might have been through effects of absorbed MA on hepatic oxidation. This might explain the quandary for a signal from enterocytes discussed by Langhans (84) that MA and cholecystokinin have similar effects on vagal discharge rate of afferents from the duodenum but opposite effects on feeding. Langhans et al (84) did report that the increase in food intake stimulated by intestinal MA infusion was eliminated by sub-diaphragmatic deafferentation; however, no evidence was presented that disconnecting afferents in this region of the vagus leaves the hepatic branch proper of the vagus nerve intact.…”

“…This might explain the quandary for a signal from enterocytes discussed by Langhans (84) that MA and cholecystokinin have similar effects on vagal discharge rate of afferents from the duodenum but opposite effects on feeding. Langhans et al (84) did report that the increase in food intake stimulated by intestinal MA infusion was eliminated by sub-diaphragmatic deafferentation; however, no evidence was presented that disconnecting afferents in this region of the vagus leaves the hepatic branch proper of the vagus nerve intact. Therefore, responses to intestinal MA infusions may well be explained by a combination of effects on gut peptide release and signalling from the liver.…”