title: Lipid transport function is the main target of oral oleoylethanolamide to reduce adiposity in high-fat-fed mice.
abstract: We evaluated the biological basis of reduced fat gain by oleoylethanolamide (OEA) in high-fat-fed mice and sought to determine how degradation of OEA affected its efficiency by comparing its effects to those of KDS-5104, a nonhydrolyzable lipid OEA analog. Mice were given OEA or KDS-5104 by the oral route (100 mg/kg body weight). Sixty-eight variables per mouse, describing six biological processes (lipid transport, lipogenesis, energy intake, energy expenditure, endocannabinoid signaling, and glucose metabolism), spanning gene expression of biochemical and physiological parameters were examined to determine the primary target whereby OEA reduces fat gain. Although KDS-5104 but not OEA was resistant to fatty acid amide hydrolase hydrolysis, OEA was degraded by an unidentified hydrolysis system in the liver. Nevertheless, both compounds equally decreased body fat pads after 5 weeks (20%; P < 0.05). The six biological functions constructed from the 68 initial variables predicted up to 58% of adipose fat variations. Lipid transport appeared central to the explanation for body fat deposition (16%; P < 0.0001), in which decreased expression of the FAT/CD36 gene was the component most related to adipose depots. Lipid transport appears to be a determinant player in the OEA fat-lowering response, with adipose tissue FAT/CD36 expression being the most relevant bioindicator of OEA action.
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UMR1260 Nutriments Lipidiques et Préventiondes Maladies Métaboliques, Marseille, France.
authors.forename: Clémentine
authors.initials: C
authors.lastname: Thabuis
authors.forename: Frédéric
authors.initials: F
authors.lastname: Destaillats
authors.forename: Didier M
authors.initials: DM
authors.lastname: Lambert
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.forename: Matthieu
authors.initials: M
authors.lastname: Maillot
authors.forename: Touafiq
authors.initials: T
authors.lastname: Harach
authors.forename: Delphine
authors.initials: D
authors.lastname: Tissot-Favre
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Martin
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects*; D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000009:adverse effects*; D019587:Dietary Supplements; D063388:Endocannabinoids; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009829:Oleic Acids / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D004041:Dietary Fats; D063388:Endocannabinoids; D009829:Oleic Acids; C488250:oleoylethanolamide