Dataset Information

Deficiency or activation of peroxisome proliferator-activated receptor ? reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice.

ABSTRACT:

Background/objectives

Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ?-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha (PPAR?). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by PPAR?.

Materials/methods

The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among PPAR? homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate (PPAR? agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA.

Results

PPAR? ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, PPAR? activation increased hepatic Acox, Fads1, Fads2 and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex.

Conclusions

LCPUFA enzyme expression was altered by PPAR?. Either PPAR? deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

SUBMITTER: Hsiao WT

PROVIDER: S-EPMC6669072 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Deficiency or activation of peroxisome proliferator-activated receptor α reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice.

Hsiao Wen-Ting WT Su Hui-Min HM Su Kuan-Pin KP Chen Szu-Han SH Wu Hai-Ping HP You Yi-Ling YL Fu Ru-Huei RH Chao Pei-Min PM

Nutrition research and practice 20190605 4

<h4>Background/objectives</h4>Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the <i>in vivo</i> conversion of α-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha (PPARα). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by PPARα.<h4>Materials/methods</h4>The tissue DHA concentrations and mRNA ...[more]

PMID: 31388404

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