title: Peroxisome Proliferator-Activated Receptor α Activation Is Not the Main Contributor to Teratogenesis Elicited by Polar Compounds from Oxidized Frying Oil.
abstract: We previously reported that polar compounds (PO) in cooking oil are teratogenic and perturbed retinoic acid (RA) metabolism. Considering PO as a potent peroxisome proliferator-activated receptor α (PPARα) activator, this study aimed to investigate the role of PPARα in PO-induced teratogenesis and disturbance of RA metabolism. Female PPARα knockout or wild type mice were mated with males of the same genotype. Pregnant mice were fed a diet containing 10% fat from either fresh oil (FO) or PO from gestational day1 to day18, and killed at day18. The PO diet significantly increased the incidence of teratogenesis and fetal RA concentrations, regardless of genotype. Though PPARα deficiency disturbed maternal RA homeostasis, itself did not contribute to teratogenesis as long as FO diet was given. The mRNA profile of genes involved in RA metabolism was differentially affected by diet or genotype in mothers and fetuses. Based on hepatic mRNA levels of genes involved in xenobiotic metabolism, we inferred that PO not only activated PPARα, but also altered transactivity of other xenobiotic receptors. We concluded that PO-induced fetal anomalies and RA accumulation were independent of PPARα activation.
authors.affiliation: Department of Nutrition, China Medical University, Taichung 404, Taiwan. chriscats211@yahoo.com.tw.
authors.forename: Yu-Shun
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department of Nutrition, China Medical University, Taichung 404, Taiwan. tingyilin1025@gmail.com.
authors.forename: Ting-Yi
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Department of Nutrition, China Medical University, Taichung 404, Taiwan. jjwu@mail.cmu.edu.tw.
authors.forename: Jia-Jiuan
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Department of Nutrition, China Medical University, Taichung 404, Taiwan. htyao@mail.cmu.edu.tw.
authors.forename: Hsien-Tsung
authors.initials: HT
authors.lastname: Yao
authors.affiliation: Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan. liyunchang@mail.cmu.edu.tw.
authors.forename: Sunny Li-Yun
authors.initials: SL
authors.lastname: Chang
authors.affiliation: Department of Nutrition, China Medical University, Taichung 404, Taiwan. pmchao@mail.cmu.edu.tw.
authors.forename: Pei-Min
authors.initials: PM
authors.lastname: Chao
mesh_terms: D000818:Animals; D004042:Dietary Fats, Unsaturated / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D010087:Oxides / Q000737:chemistry; D047493:PPAR alpha / Q000172:deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects; D064793:Teratogenesis / Q000187:drug effects / Q000235:genetics; D013723:Teratogens / Q000737:chemistry / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology
chemical_list: D004042:Dietary Fats, Unsaturated; D010087:Oxides; D047493:PPAR alpha; D012333:RNA, Messenger; D013723:Teratogens; D014801:Vitamin A
keywords: PPARα; oxidized frying oil; polar compounds; retinoic acid; teratogenesis