Clofibric acid increases molecular species of phosphatidylethanolamine containing arachidonic acid for biogenesis of peroxisomal membranes in peroxisome proliferation in the liver

Miura, Hiroaki; Mizuguchi, Hiroki; Amano-Iwashita, Mino; Maeda-Kogure, Rie; Negishi, Akio; Sakai, Ayako; Toyama, Tomoaki; Kawai, Hiroshi; Mitsumoto, Atsushi; Kudo, Naomi

doi:10.1016/j.bbalip.2021.158963

Cited by 6 publications

(6 citation statements)

References 70 publications

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“…Several proteins associated with the arachidonic acid (AA) metabolism pathway were also differentially regulated. It was recently shown that the PPARα agonist, clofibrate, increases molecular species of phosphatidylethanolamine containing arachidonic acid for biogenesis of peroxisomal membranes in peroxisome proliferation in the liver [23]. The downregulated monooxygenase Cyp4f14, orthologue for human CYP4F12, is involved in the ω-hydroxylation of arachidonic acid to 20hydroxyeicosatetraenoic acid [24], while Cyp2b9, also downregulated, is the orthologue for humans CYP2B6, and involved in arachidonic acid epoxidation [25].…”

Section: Discussionmentioning

confidence: 99%

Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of ω-Oxidation

Khalil

Carrino

Lin

et al. 2022

IJMS

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Peroxisomal fatty acid α-oxidation is an essential pathway for the degradation of β-carbon methylated fatty acids such as phytanic acid. One enzyme in this pathway is 2-hydroxyacyl CoA lyase (HACL1), which is responsible for the cleavage of 2-hydroxyphytanoyl-CoA into pristanal and formyl-CoA. Hacl1 deficient mice do not present with a severe phenotype, unlike mice deficient in other α-oxidation enzymes such as phytanoyl-CoA hydroxylase deficiency (Refsum disease) in which neuropathy and ataxia are present. Tissues from wild-type and Hacl1−/− mice fed a high phytol diet were obtained for proteomic and lipidomic analysis. There was no phenotype observed in these mice. Liver, brain, and kidney tissues underwent trypsin digestion for untargeted proteomic liquid chromatography-mass spectrometry analysis, while liver tissues also underwent fatty acid hydrolysis, extraction, and derivatisation for fatty acid gas chromatography-mass spectrometry analysis. The liver fatty acid profile demonstrated an accumulation of phytanic and 2-hydroxyphytanic acid in the Hacl1−/− liver and significant decrease in heptadecanoic acid. The liver proteome showed a significant decrease in the abundance of Hacl1 and a significant increase in the abundance of proteins involved in PPAR signalling, peroxisome proliferation, and omega oxidation, particularly Cyp4a10 and Cyp4a14. In addition, the pathway associated with arachidonic acid metabolism was affected; Cyp2c55 was upregulated and Cyp4f14 and Cyp2b9 were downregulated. The kidney proteome revealed fewer significantly upregulated peroxisomal proteins and the brain proteome was not significantly different in Hacl1−/− mice. This study demonstrates the powerful insight brought by proteomic and metabolomic profiling of Hacl1−/− mice in better understanding disease mechanism in fatty acid α-oxidation disorders.

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Section: Discussionmentioning

confidence: 99%

Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of ω-Oxidation

Khalil

Carrino

Lin

et al. 2022

IJMS

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“…There were reports that excess consumption of lysoPCs regulates a variety of biological processes, including cell proliferation and in ammation. Peroxisomes are dynamic organelles surrounded by a single membrane with a de ned lipid composition, the major components of which are phosphatidylcholine (PC) and phosphatidylethanolamine (PE) [37]. Besides, PC and PE are important supporting nutrients for the liver, exert an obvious protective effect against liver damage from viruses, pharmaceuticals, alcoholism, and other toxic in uences [36,38].…”

Section: Discussionmentioning

confidence: 99%

The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats

Chen

Huang

et al. 2022

Inflammation

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The present study was to investigate the therapeutical effects and mechanisms of Asiatic acid from Potentilla Chinensis against alcoholic hepatitis. Rats were intragastrically fed with alcohol for 12 weeks to induce alcoholic hepatitis and then treated with various drugs for further 12 weeks. The results showed that Asiatic acid signi cantly alleviated liver injury caused by alcohol in rats, as evidenced by the improved histological changes and the lower levels of AST, ALT, and TBIL. Besides, Asiatic acid signi cantly enhanced the activity of ADH and ALDH, promoting alcohol metabolism. Asiatic acid suppressed CYP2E1 activity and NADP + /NADPH ratio, resulting in low ROS production. Further study revealed that Asiatic acid markedly reduced hepatocyte apoptosis by regulating the expression levels of the caspase and Bcl-2 families. Moreover, Asiatic acid could regulate the Keap1/Nrf2 and NF-κB signaling pathway, attenuating oxidative stress and in ammation as a result. Interestingly, the comprehensive analysis of transcriptomics and metabolomics indicated that Asiatic acid regulated the gene expression of Gpat4 and thereby affected the biosynthesis of the metabolites (1-acyl-Sn-glycerol-3-phosphocholine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine), regulating the glycerophospholipid metabolism pathway and ultimately ameliorating hepatocyte damage. In conclusion, this study demonstrates that Asiatic acid can ameliorate alcoholic hepatitis by modulating the NF-κB and Keap1/Nrf2 signaling pathways and the glycerophospholipid metabolism pathway, which may be developed as a potential medicine for the treatment of alcoholic hepatitis.

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“…This finding is consistent with our observations. Increased PE fraction breakdown could release arachidonic acid, which would be accompanied by lower quantities of bile acids in the serum of patients with psoriasis, as well as poorer antioxidant indicators, such as glutathione (Sorokin et al, 2018;Miura et al, 2021). We also found higher Cer levels in patients with only PV than HCs, but their levels were still lower than those of patients with PV and metabolic diseases, suggesting that Cer may contribute to metabolic and inflammatory responses.…”

Section: Discussionmentioning

confidence: 64%

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Clofibric acid increases molecular species of phosphatidylethanolamine containing arachidonic acid for biogenesis of peroxisomal membranes in peroxisome proliferation in the liver

Cited by 6 publications

References 70 publications

Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of ω-Oxidation

Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of ω-Oxidation

The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats

Table6.XLSX

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