title: High dietary fat intake influences the activation of specific hindbrain and hypothalamic nuclei by the satiety factor oleoylethanolamide.
abstract: Chronic exposure to a diet rich in fats changes the gastrointestinal milieu and alters responses to several signals involved in the control of food intake. Oleoylethanolamide (OEA) is a gut-derived satiety signal released from enterocytes upon the ingestion of dietary fats. The anorexigenic effect of OEA, which requires intestinal PPAR-alpha receptors and is supposedly mediated by vagal afferents, is associated with the induction of c-fos in several brain areas involved in the control of food intake, such as the nucleus of the solitary tract (NST) and the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). In the present study we investigated whether the exposure to a high fat diet (HFD) alters the hindbrain and hypothalamic responses to OEA. To this purpose we evaluated the effects of OEA at a dose that reliably inhibits eating (10mg/kg i.p.) on the induction of c-fos in the NST, area postrema (AP), PVN and SON in rats maintained either on standard chow or a HFD. We performed a detailed analysis of the different NST subnuclei activated by i.p. OEA and found that peripheral OEA strongly activates c-fos expression in the AP, NST and in the hypothalamus of both chow and HFD fed rats. The extent of c-fos expression was, however, markedly different between the two groups of rats, with a weaker activation of selected NST subnuclei and stronger activation of the PVN in HFD-fed than in chow-fed rats. HFD-fed rats were also more sensitive to the immediate hypophagic action of OEA than chow-fed rats. These effects may be due to a decreased sensitivity of vagal afferent fibers that might mediate OEA's actions on the brain and/or an altered sensitivity of brain structures to OEA.
authors.affiliation: Dept. of Physiology and Pharmacology "V. Erspamer", Sapienza Univ. of Rome, 00185 Rome, Italy. Electronic address: adeleromano.uniroma1@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Romano
authors.affiliation: Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Karimian Azari
authors.affiliation: Dept. of Physiology and Pharmacology "V. Erspamer", Sapienza Univ. of Rome, 00185 Rome, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Tempesta
authors.affiliation: Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Mansouri
authors.affiliation: School of Pharmacy, Italy.
authors.forename: M V
authors.initials: MV
authors.lastname: Micioni Di Bonaventura
authors.affiliation: Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Ramachandran
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty, and Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: T A
authors.initials: TA
authors.lastname: Lutz
authors.affiliation: Dept. of Physiology and Pharmacology "V. Erspamer", Sapienza Univ. of Rome, 00185 Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bedse
authors.affiliation: Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Langhans
authors.affiliation: Dept. of Physiology and Pharmacology "V. Erspamer", Sapienza Univ. of Rome, 00185 Rome, Italy. Electronic address: silvana.gaetani@uniroma1.it.
authors.forename: S
authors.initials: S
authors.lastname: Gaetani
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects*; D063388:Endocannabinoids; D005786:Gene Expression Regulation / Q000187:drug effects*; D007032:Hypothalamus, Anterior / Q000187:drug effects*; D008297:Male; D009829:Oleic Acids / Q000494:pharmacology*; D010121:Oxytocin / Q000235:genetics / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects*; D013495:Supraoptic Nucleus / Q000187:drug effects; D013997:Time Factors
chemical_list: D063388:Endocannabinoids; D009829:Oleic Acids; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C488250:oleoylethanolamide; D010121:Oxytocin
keywords: Food intake; Gut-brain axis; High fat diet; Hindbrain; Hypothalamus; Oleoylethanolamide