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  • Plenary
  • M1.04 - The PPARalpha agonist, fenofibrate decreases levels of anorectic N-acylethanolamines in the small intestine of mice

    Sunday, June 29, 2014 6:26 PM - Sunday, June 29, 2014 6:28 PM

    • Harald S. Hansen, Department of Drug Design & Pharmacology, University of Copenhagen, Denmark ;
    • Thi Ai Diep, Department of Drug Design & Pharmacology, University of Copenhagen, Denmark ;
    • Golfam Golbaz, Department of Drug Design & Pharmacology, University of Copenhagen, Denmark
    Harald S. Hansen, Department of Drug Design & Pharmacology, University of Copenhagen, Denmark; Thi Ai Diep, Department of Drug Design & Pharmacology, University of Copenhagen, Denmark; Golfam Golbaz, Department of Drug Design & Pharmacology, University of Copenhagen, Denmark;

    The anorectic N-acylethanolamines (NAEs), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and linoleoylethanolamide (LEA) are generated in the small intestine where they may function as a homeostatic signal, which contributes to regulating the amount and type of food ingested (1, 2). Their mechanism of action involves activation of PPARalpha and of the vagus nerve (2). We have previously shown that a prolonged intake of a diet high in fat (45E% fat) will decrease the intestinal levels of these signaling lipids in a time and dose-dependent manner (3,4), suggesting that this effect may contribute to the hyperphagic effect of dietary fat. Male C57BL/6 mice were fed with either chow (minced Altromin) (n=8 from Taconic and n=8 from Charles River) or chow mixed with supplemented 0.5 wt% Fenofibrate (n=8 from Taconic and n=8 from Charles River) for seven days, and intestinal levels of NAEs were measured by LC-MS as previously described (3,4). The levels of PEA and LEA were significantly decreased (23-64%) in both strain of mice , while the decrease in OEA only reached significance in Charles river mice. There was no difference in levels of anandamide in any strain of mice. This suggests that PPARalpha may be the fat-sensing receptor in the intestine being responsible for the fat-induced decrease in the level of anorectic OEA, PEA and LEA.

    1) Piomelli D (2013) Trends Endocrinol Metab 24;332-341

    2) Tellez LA et al (2013) Science 341;800-802

    3) Artmann A et al (2008) Biochim Biophys Acta 1781;200-212

    4) Diep TA et al (2011) FASEB J 25;765-774