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Dysregulated expression of fatty acid oxidation enzymes and iron-regulatory genes in livers of Nrf2-null mice.
J Gastroenterol Hepatol. 2012 Nov; 27(11):1711-7.JG

Abstract

BACKGROUND AND AIM

Hepatic excessive iron may play a role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Nrf2 is a master regulator of antioxidative responses. However, the role of Nrf2 in lipid and iron homeostasis remains unclear. Accordingly, it was examined how Nrf2 regulates lipid-related and iron-regulatory genes after feeding a high-fat diet (HFD) with iron.

METHODS

Wild-type and Nrf2-null mice were fed the following diets: (i) control diet (4% soybean oil) for 12 weeks, (ii) control diet for 8 weeks followed by control diet containing 0.5% carbonyl iron for 4 weeks, (iii) HFD (4% soybean oil and 16% lard) for 12 weeks, (iv) HFD for 8 weeks followed by HFD containing 0.5% carbonyl iron for 4 weeks. Blood and livers were removed after 12 weeks.

RESULTS

Nrf2-null control mice exhibited a tendency towards higher hepatic triglycerides compared to wild-type control mice. Hepatic malondialdehyde was higher and hepatic iron levels tended to be higher in Nrf2-null mice than wild-type counterparts while on a HFD. The HFD with iron synergistically induced mRNA expression of Pparα targets, including Acox and Cpt1 in wild-type mice, yet the induction was diminished in Nrf2-null mice. Hepatic hepcidin and ferroportin 1 mRNA expression were increased in wild-type mice after feeding a HFD with iron, but were unchanged in any group of Nrf2-null mice.

CONCLUSIONS

Nrf2 deletion dysregulates hepatic mRNA expression of β-oxidation enzymes and iron-related genes, possibly causing a trend for increased hepatic triglyceride and iron concentrations. Nrf2 may have roles in the progression of NASH.

Authors+Show Affiliations

Department of Clinical Laboratory Medicine, Kinki University Faculty of Medicine, Osakasayama, Japan. ytanaka@med.kindai.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22591204

Citation

Tanaka, Yuji, et al. "Dysregulated Expression of Fatty Acid Oxidation Enzymes and Iron-regulatory Genes in Livers of Nrf2-null Mice." Journal of Gastroenterology and Hepatology, vol. 27, no. 11, 2012, pp. 1711-7.
Tanaka Y, Ikeda T, Yamamoto K, et al. Dysregulated expression of fatty acid oxidation enzymes and iron-regulatory genes in livers of Nrf2-null mice. J Gastroenterol Hepatol. 2012;27(11):1711-7.
Tanaka, Y., Ikeda, T., Yamamoto, K., Ogawa, H., & Kamisako, T. (2012). Dysregulated expression of fatty acid oxidation enzymes and iron-regulatory genes in livers of Nrf2-null mice. Journal of Gastroenterology and Hepatology, 27(11), 1711-7. https://doi.org/10.1111/j.1440-1746.2012.07180.x
Tanaka Y, et al. Dysregulated Expression of Fatty Acid Oxidation Enzymes and Iron-regulatory Genes in Livers of Nrf2-null Mice. J Gastroenterol Hepatol. 2012;27(11):1711-7. PubMed PMID: 22591204.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dysregulated expression of fatty acid oxidation enzymes and iron-regulatory genes in livers of Nrf2-null mice. AU - Tanaka,Yuji, AU - Ikeda,Takanori, AU - Yamamoto,Kazuo, AU - Ogawa,Hiroshi, AU - Kamisako,Toshinori, PY - 2012/5/18/entrez PY - 2012/5/18/pubmed PY - 2013/5/10/medline SP - 1711 EP - 7 JF - Journal of gastroenterology and hepatology JO - J Gastroenterol Hepatol VL - 27 IS - 11 N2 - BACKGROUND AND AIM: Hepatic excessive iron may play a role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Nrf2 is a master regulator of antioxidative responses. However, the role of Nrf2 in lipid and iron homeostasis remains unclear. Accordingly, it was examined how Nrf2 regulates lipid-related and iron-regulatory genes after feeding a high-fat diet (HFD) with iron. METHODS: Wild-type and Nrf2-null mice were fed the following diets: (i) control diet (4% soybean oil) for 12 weeks, (ii) control diet for 8 weeks followed by control diet containing 0.5% carbonyl iron for 4 weeks, (iii) HFD (4% soybean oil and 16% lard) for 12 weeks, (iv) HFD for 8 weeks followed by HFD containing 0.5% carbonyl iron for 4 weeks. Blood and livers were removed after 12 weeks. RESULTS: Nrf2-null control mice exhibited a tendency towards higher hepatic triglycerides compared to wild-type control mice. Hepatic malondialdehyde was higher and hepatic iron levels tended to be higher in Nrf2-null mice than wild-type counterparts while on a HFD. The HFD with iron synergistically induced mRNA expression of Pparα targets, including Acox and Cpt1 in wild-type mice, yet the induction was diminished in Nrf2-null mice. Hepatic hepcidin and ferroportin 1 mRNA expression were increased in wild-type mice after feeding a HFD with iron, but were unchanged in any group of Nrf2-null mice. CONCLUSIONS: Nrf2 deletion dysregulates hepatic mRNA expression of β-oxidation enzymes and iron-related genes, possibly causing a trend for increased hepatic triglyceride and iron concentrations. Nrf2 may have roles in the progression of NASH. SN - 1440-1746 UR - https://www.unboundmedicine.com/medline/citation/22591204/Dysregulated_expression_of_fatty_acid_oxidation_enzymes_and_iron_regulatory_genes_in_livers_of_Nrf2_null_mice_ L2 - https://doi.org/10.1111/j.1440-1746.2012.07180.x DB - PRIME DP - Unbound Medicine ER -