title: DHA attenuates postprandial hyperlipidemia via activating PPARα in intestinal epithelial cells.
abstract: It is known that peroxisome proliferator-activated receptor (PPAR)α, whose activation reduces hyperlipidemia, is highly expressed in intestinal epithelial cells. Docosahexaenoic acid (DHA) could improve postprandial hyperlipidemia, however, its relationship with intestinal PPARα activation is not revealed. In this study, we investigated whether DHA can affect postprandial hyperlipidemia by activating intestinal PPARα using Caco-2 cells and C57BL/6 mice. The genes involved in fatty acid (FA) oxidation and oxygen consumption rate were increased, and the secretion of triacylglyceride (TG) and apolipoprotein B (apoB) was decreased in DHA-treated Caco-2 cells. Additionally, intestinal FA oxidation was induced, and TG and apoB secretion from intestinal epithelial cells was reduced, resulting in the attenuation of plasma TG and apoB levels after oral administration of olive oil in DHA-rich oil-fed mice compared with controls. However, no increase in genes involved in FA oxidation was observed in the liver. Furthermore, the effects of DHA on intestinal lipid secretion and postprandial hyperlipidemia were abolished in PPARα knockout mice. In conclusion, the present work suggests that DHA can inhibit the secretion of TG from intestinal epithelial cells via PPARα activation, which attenuates postprandial hyperlipidemia.
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Rino
authors.initials: R
authors.lastname: Kimura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Shan
authors.initials: S
authors.lastname: Lin
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.forename: Kaeko
authors.initials: K
authors.lastname: Murota
authors.forename: Rieko
authors.initials: R
authors.lastname: Nakata
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Inoue
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D018938:Caco-2 Cells; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism*; D019518:Postprandial Period / Q000187:drug effects*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D005227:Fatty Acids; D047493:PPAR alpha; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D010100:Oxygen
keywords: cardiovascular diseases; docosahexaenoic acid; dyslipidemia; fatty acid oxidation; peroxisome proliferator-activated receptor α; polyunsaturated fatty acid; small intestine; triacylglyceride