Anti-inflammatory effect of palmitoylethanolamide on human adipocytes.
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.
Hoareau
Laurence
L
Laboratoire de Biochimie et Génétique Moléculaire, Université de La Réunion, Saint-Denis, France.
Buyse
Marion
M
Festy
Franck
F
Ravanan
Palaniyandi
P
Gonthier
Marie-Paule
MP
Matias
Isabel
I
Petrosino
Stefania
S
Tallet
Frank
F
d'Hellencourt
Christian Lefebvre
CL
Cesari
Maya
M
Di Marzo
Vincenzo
V
Roche
Régis
R
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*
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