title: Palmitoylethanolamide prevents metabolic alterations and restores leptin sensitivity in ovariectomized rats.
abstract: It has been suggested a role of fatty acid ethanolamides in control of feeding behavior. Among these, palmitoylethanolamide (PEA) has not been directly implicated in appetite regulation and weight gain. The aim of this study was to investigate the effect of PEA on food intake and body weight and the interaction between PEA and hypothalamic leptin signaling in ovariectomized rats. Ovariectomy produced hyperphagia and increased weight gain, making it an useful model of mild obesity. Ovariectomized rats were treated with PEA (30 mg/kg sc) for 5 weeks. Then, blood was collected, and hypothalamus and adipose tissue were removed for histological, cellular, and molecular measurements. We showed that PEA caused a reduction of food intake, body weight, and fat mass. The mechanisms underlying PEA effects involved an improvement in hypothalamic leptin signaling, through a raise in signal transducer and activator of transcription 3 phosphorylation. We also reported that PEA reduced AMP-activated protein kinase-α phosphorylation and modulated transcription of anorectic and orexigenic neuropeptides in the hypothalamus. Moreover, PEA increased AMP-activated protein kinase-α phosphorylation and carnitine palmitoyltransferase 1 transcription in adipose tissue, suggesting an increase in ATP-producing catabolic pathway. PEA also polarized adipose tissue macrophages to M2 lean phenotype, associated to a reduction of inflammatory cytokines/adipokines. To demonstrate the direct effect of PEA on leptin sensitivity without interference of adiposity loss, we obtained consistent data in PEA-treated sham-operated animals and in vitro in SH-SY5Y neuroblastoma cell line. Therefore, our data provide a rationale for the therapeutic use of PEA in obese postmenopausal woman.
authors.affiliation: Department of Pharmacy (G.M.R., A.S., R.R., R.S., A.C., R.M.), University of Naples "Federico II", Naples, 80131, Italy; Department of Pathology and Animal Health (O.P.), University of Naples "Federico II", Naples, 80137, Italy; Department of Neurosciences, Odontostomatologic and Reproductive Sciences (C.D.C.), University of Naples "Federico II" Naples 80131, Italy; and Department of Obstetrics, Gynecology, and Reproductive Sciences (S.D.), Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: G
authors.initials: G
authors.lastname: Mattace Raso
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: R
authors.initials: R
authors.lastname: Russo
authors.forename: R
authors.initials: R
authors.lastname: Simeoli
authors.forename: O
authors.initials: O
authors.lastname: Paciello
authors.forename: C
authors.initials: C
authors.lastname: Di Carlo
authors.forename: S
authors.initials: S
authors.lastname: Diano
authors.forename: A
authors.initials: A
authors.lastname: Calignano
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meli
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D054392:Adipokines / Q000378:metabolism; D000577:Amides / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D001835:Body Weight; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D063388:Endocannabinoids / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry; D004983:Ethanolamines / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry; D005247:Feeding Behavior; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010052:Ovariectomy; D010169:Palmitic Acids / Q000737:chemistry*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D015430:Weight Gain
chemical_list: D054392:Adipokines; D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D063388:Endocannabinoids; D004983:Ethanolamines; D005227:Fatty Acids; D020738:Leptin; D010169:Palmitic Acids; D000431:Ethanol; C005958:palmidrol; D000255:Adenosine Triphosphate