[PDF][PDF] Vagal afferents are not necessary for the satiety effect of the gut lipid messenger oleoylethanolamide

EK Azari, D Ramachandran, S Weibel… - Am J Physiol Regul …, 2014 - academia.edu
Am J Physiol Regul Integr Comp Physiol, 2014academia.edu
First published May 14, 2014; doi: 10.1152/ajpregu. 00067.2014.—The endogenous lipid
messenger oleoylethanolamide (OEA) inhibits eating and modulates fat metabolism
supposedly through the activation of peroxisome proliferator-activated receptor-(PPAR) and
vagal sensory fibers. We tested in adult male rats whether OEA stimulates fatty acid
oxidation (FAO) and ketogenesis and whether it increases plasma levels of the satiating gut
peptides glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We also explored whether …
First published May 14, 2014; doi: 10.1152/ajpregu. 00067.2014.—The endogenous lipid messenger oleoylethanolamide (OEA) inhibits eating and modulates fat metabolism supposedly through the activation of peroxisome proliferator-activated receptor-(PPAR) and vagal sensory fibers. We tested in adult male rats whether OEA stimulates fatty acid oxidation (FAO) and ketogenesis and whether it increases plasma levels of the satiating gut peptides glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We also explored whether OEA still inhibits eating after subdiaphragmatic vagal deafferentation (SDA). We found that intraperitoneally injected OEA (10 mg/kg body wt) reduced (P 0.05) food intake mainly by increasing meal latency and that this effect was stronger in rats fed a 60% high-fat diet (HFD) than in chow-fed rats. OEA increased (P 0.05) postprandial plasma nonesterified fatty acids and-hydroxybutyrate (BHB) in the hepatic portal vein (HPV) and vena cava (VC) 30 min after injection, which was more pronounced in HFD-than in chow-fed rats. OEA also increased the protein expression of the key ketogenetic enzyme, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, in the jejunum of HFD-fed rats, but not in the liver or duodenum of either diet group. Furthermore, OEA decreased GLP-1 and PYY concentrations (P 0.05) in the HPV and VC 30 min after administration. Finally, OEA reduced food intake in SDA and sham-operated rats similarly. Our findings indicate that neither intact abdominal vagal afferents nor prandial increases in GLP-1 or PYY are necessary for the satiety effect of OEA. The enhanced FAO and ketogenesis raise the possibility of an involvement of intestine-derived BHB in OEA’s satiety effect under certain conditions. ketogenesis; small intestine; food intake; fatty acid oxidation; gut peptides
THE SMALL INTESTINE PLAYS a key role in the regulation of energy balance and fat homeostasis (1, 34). Digestion, absorption, and intracellular processing of dietary fat in the small intestine trigger the release of gut hormones that inhibit eating, such as CCK, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and apolipoprotein A-IV (1, 68). The intestine also releases other signaling substances that are implicated in the control of eating (26, 48), ie, fatty acid ethanolamides, such as anandamide, palmitoylethanolamide, linoylethanolamide, and oleoylethanolamide (OEA). OEA, the amide of ethanolamine and oleic acid, potently reduces food intake without inducing visceral illness or anxiety, suggesting that it has a specific inhibitory effect on eating (44, 46, 48). The exact mechanism by which OEA inhibits eating is still poorly under-
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