Vagal afferents are not necessary for the satiety effect of the gut lipid messenger oleoylethanolamide.
The endogenous lipid messenger oleoylethanolamide (OEA) inhibits eating and modulates fat metabolism supposedly through the activation of peroxisome proliferator-activated receptor-α (PPARα) 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 β-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
Elnaz Karimian
EK
Azari
Deepti
D
Ramachandran
Sandra
S
Weibel
Myrtha
M
Arnold
Adele
A
Romano
Silvana
S
Gaetani
Wolfgang
W
Langhans
Abdelhak
A
Mansouri
D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D063388:Endocannabinoids; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009829:Oleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012527:Satiation / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000601:surgery
D063388:Endocannabinoids; D009829:Oleic Acids; C488250:oleoylethanolamide; D052216:Glucagon-Like Peptide 1