Peroxisome Proliferator-Activated Receptor α Activation Is Not the Main Contributor to Teratogenesis Elicited by Polar Compounds from Oxidized Frying Oil.

Yu-Shun Lin,Jia-Jiuan Wu,Pei-Min Chao,Ting-Yi Lin,Sunny Chang,Hsien-Tsung Yao

doi:10.3390/ijms18030510

Yu-Shun Lin, Jia-Jiuan Wu + Show 4 more

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https://doi.org/10.3390/ijms18030510

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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.

Highlights

Many environmental contaminants and chemicals are known to cause developmental toxicity, with warnings given to women of childbearing age [1,2]
We recently reported that Oxidized frying oil (OFO), the polar fraction or polar compounds (PO), is teratogenic, and that this effect was associated with disturbed retinoic acid (RA) metabolism in pregnant mice and their fetuses [4]
We previously reported that PO is a major contributor to peroxisome proliferator-activated receptor α(PPARα) activation by OFO [4]

Summary

Introduction

Many environmental contaminants and chemicals (including heavy metals, polychlorinated biphenyls, radiation, and illicit drugs) are known to cause developmental toxicity, with warnings given to women of childbearing age [1,2]. We know little regarding potential risks associated with foods. Oxidized frying oil (OFO) is essentially an environmental pollutant that can be regarded as a xenobiotic since it is foreign to the body, lipophilic and induces expression of detoxifying CYP450 monoxygenase and phase II conjugation enzymes to facilitate its own catabolism [3]. We recently reported that OFO, the polar fraction or polar compounds (PO), is teratogenic, and that this effect was associated with disturbed retinoic acid (RA) metabolism in pregnant mice and their fetuses [4]. Underlying mechanisms of disturbed RA metabolic gene expression by PO remain unknown. It is noteworthy that RA is a well-characterized morphogen; by binding to the RA receptor (RAR) and retinoid X receptor (RXR), it controls a network of genes (e.g., homeobox gene HoxB1)

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