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Lipid transport function is the main target of oral oleoylethanolamide to reduce adiposity in high-fat-fed mice

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Thabuis, Clémentine Destaillats, Frédéric Lambert, Didier [UCL] Muccioli, Giulio [UCL] Maillot, Matthieu Martin, Jean-Charles

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.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès libre
Publication date 2011
Language Anglais
Journal information "Journal of Lipid Research" - Vol. 52, no. 7, p. 1373-82 (2011)
Peer reviewed yes
Publisher American Society for Biochemistry and Molecular Biology, Inc. ((United States) Bethesda, MD.)
issn 0022-2275
e-issn 1539-7262
Publication status Publié
Affiliation UCL - SSS/LDRI - Louvain Drug Research Institute
MESH Subject Adipose Tissue - drug effects, metabolism ; Adiposity - drug effects ; Mice ; Mice, Inbred C57BL ; Oleic Acids - administration & dosage, pharmacology ; Administration, Oral ; Animals ; Biological Transport - drug effects ; Body Weight - drug effects ; Dietary Fats - adverse effects ; Dietary Supplements ; Lipid Metabolism - drug effects ; Male
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Bibliographic reference Thabuis, Clémentine ; Destaillats, Frédéric ; Lambert, Didier ; Muccioli, Giulio ; Maillot, Matthieu ; et. al. Lipid transport function is the main target of oral oleoylethanolamide to reduce adiposity in high-fat-fed mice. In: Journal of Lipid Research, Vol. 52, no. 7, p. 1373-82 (2011)
Permanent URL http://hdl.handle.net/2078.1/106001