title: Anti-inflammatory effect of palmitoylethanolamide on human adipocytes.
abstract: Obesity leads to the appearance of an inflammatory process, which can be initiated even with a moderate weight gain. Palmitoylethanolamide (PEA) is an endogenous lipid, secreted by human adipocytes, that possesses numerous anti-inflammatory properties. The main purpose of this study was to investigate the anti-inflammatory effect of PEA on human adipocytes, as well as in a murine model. The production of tumor necrosis factor-alpha (TNF-alpha) by lipopolysaccharide (LPS)-treated human subcutaneous adipocytes in primary culture and CF-1 mice was investigated by enzyme-linked immunosorbent assay. The effects of PEA on adipocyte TNF-alpha secretion were explored as well as some suspected PEA anti-inflammatory pathways: nuclear factor-kappaB (NF-kappaB) pathway, peroxisome proliferator-activated receptor-alpha (PPAR-alpha) gene expression, and TNF-alpha-converting enzyme (TACE) activity. The effects of PEA on the TNF-alpha serum concentration in intraperitoneally LPS-treated mice were also studied. We demonstrate that the LPS induced secretion of TNF-alpha by human adipocytes is inhibited by PEA. This action is neither linked to a reduction in TNF-alpha gene transcription nor to the inhibition of TACE activity. Moreover, PPAR-alpha is not implicated in this anti-inflammatory activity. Lastly, PEA exhibits a wide-reaching anti-inflammatory action as the molecule is able to completely inhibit the strong increase in TNF-alpha levels in the serum of mice treated with high doses of LPS. In view of its virtual lack of toxicity, PEA might become a potentially interesting candidate molecule in the prevention of obesity-associated insulin resistance.
authors.affiliation: Laboratoire de Biochimie et Génétique Moléculaire, Université de La Réunion, Saint-Denis, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Hoareau
authors.forename: Marion
authors.initials: M
authors.lastname: Buyse
authors.forename: Franck
authors.initials: F
authors.lastname: Festy
authors.forename: Palaniyandi
authors.initials: P
authors.lastname: Ravanan
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Gonthier
authors.forename: Isabel
authors.initials: I
authors.lastname: Matias
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Frank
authors.initials: F
authors.lastname: Tallet
authors.forename: Christian Lefebvre
authors.initials: CL
authors.lastname: d'Hellencourt
authors.forename: Maya
authors.initials: M
authors.lastname: Cesari
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Régis
authors.initials: R
authors.lastname: Roche
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000328:Adult; D000577:Amides; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004983:Ethanolamines; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D010169:Palmitic Acids / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D063388:Endocannabinoids; D004983:Ethanolamines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047493:PPAR alpha; D010169:Palmitic Acids; D014409:Tumor Necrosis Factor-alpha; C005958:palmidrol; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse