title: Activation of peroxisome proliferator-activated receptor-α (PPARα) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes.
abstract: Activation of peroxisome proliferator-activated receptor (PPAR)-α which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPARα activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPARα activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPARα agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and production of CO(2) and acid soluble metabolites in enterocytes. Moreover, bezafibrate treatment suppressed postprandial lipidemia after oral administration of olive oil to the mice. These findings indicate that PPARα activation suppresses postprandial lipidemia through enhancement of fatty acid oxidation in enterocytes, suggesting that intestinal lipid metabolism regulated by PPARα activity is a novel target of PPARα agonist for decreasing circulating levels of lipids under postprandial conditions.
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Rino
authors.initials: R
authors.lastname: Kimura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Kaeko
authors.initials: K
authors.lastname: Murota
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Saori
authors.initials: S
authors.lastname: Niiya
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kanzaki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Moriyama
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D000818:Animals; D001629:Bezafibrate / Q000008:administration & dosage*; D018938:Caco-2 Cells; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000819:agonists*; D019518:Postprandial Period; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D014280:Triglycerides; D001629:Bezafibrate