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Nrf2 deletion causes "benign" simple steatosis to develop into nonalcoholic steatohepatitis in mice fed a high-fat diet.
Lipids Health Dis. 2013 Nov 04; 12:165.LH

Abstract

BACKGROUND

Nonalcoholic fatty liver disease begins with the aberrant accumulation of triglyceride in the liver. Its spectrum includes the earliest stage of hepatic simple steatosis (SS), nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Generally, hepatic SS is often self-limited; however 10%-30% of patients with hepatic SS progress to NASH. The cause(s) of the transition from SS to NASH are unclear. We aimed to test the contribution of nuclear erythroid 2-related factor 2 (Nrf2) on the progression of "benign" SS to NASH in mice fed a high fat diet. In doing so, we discovered the influence of fatty acid in that progression.

METHOD

The involvement of Nrf2 in defending against the development of NASH was studied in an experimental model induced by a high-fat diet. Wild-type and Nrf2-null mice were fed the diet. Their specimens were analyzed for pathology as well as for fatty acid content and ratios.

RESULT

In feeding the high-fat diet to the Wild-type and the Nrf2-null mice, the Wild-type mice increased hepatic fat deposition without inflammation or fibrosis (i.e., simple steatosis), while the Nrf2-null mice had significantly more hepatic steatosis and substantial inflammation, (i.e., nonalcoholic steatohepatitis). In addition, as a result of the high-fat diet, SFA (C20: 0, C22: 0) and MUFA (C18: 1, C20: 1) content in Nrf2-null mice were significantly higher than in Wild-type mice. In the Nrf2-null mice the PUFA/TFA ratio decreased; conversely, the MUFA/TFA ratio increased.

CONCLUSION

The deletion of Nrf2 causes "benign" SS to develop into NASH in mice fed with a high-fat diet, through prompt fatty acid accumulation and disruption of hepatic fatty acid composition in the liver.

Authors+Show Affiliations

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableDepartment of Basic Veterinary Science, College of Veterinary Medicine Northeast Agricultural University, Harbin, Heilongjiang 150030, China. zhangxiuying@neau.edu.cn.

Pub Type(s)

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

Language

eng

PubMed ID

24188280

Citation

Wang, Chunhua, et al. "Nrf2 Deletion Causes "benign" Simple Steatosis to Develop Into Nonalcoholic Steatohepatitis in Mice Fed a High-fat Diet." Lipids in Health and Disease, vol. 12, 2013, p. 165.
Wang C, Cui Y, Li C, et al. Nrf2 deletion causes "benign" simple steatosis to develop into nonalcoholic steatohepatitis in mice fed a high-fat diet. Lipids Health Dis. 2013;12:165.
Wang, C., Cui, Y., Li, C., Zhang, Y., Xu, S., Li, X., Li, H., & Zhang, X. (2013). Nrf2 deletion causes "benign" simple steatosis to develop into nonalcoholic steatohepatitis in mice fed a high-fat diet. Lipids in Health and Disease, 12, 165. https://doi.org/10.1186/1476-511X-12-165
Wang C, et al. Nrf2 Deletion Causes "benign" Simple Steatosis to Develop Into Nonalcoholic Steatohepatitis in Mice Fed a High-fat Diet. Lipids Health Dis. 2013 Nov 4;12:165. PubMed PMID: 24188280.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nrf2 deletion causes "benign" simple steatosis to develop into nonalcoholic steatohepatitis in mice fed a high-fat diet. AU - Wang,Chunhua, AU - Cui,Yizhe, AU - Li,Chunyan, AU - Zhang,Yanhua, AU - Xu,Shang, AU - Li,Xiaochong, AU - Li,Hong, AU - Zhang,Xiuying, Y1 - 2013/11/04/ PY - 2013/09/29/received PY - 2013/10/31/accepted PY - 2013/11/6/entrez PY - 2013/11/6/pubmed PY - 2014/7/9/medline SP - 165 EP - 165 JF - Lipids in health and disease JO - Lipids Health Dis VL - 12 N2 - BACKGROUND: Nonalcoholic fatty liver disease begins with the aberrant accumulation of triglyceride in the liver. Its spectrum includes the earliest stage of hepatic simple steatosis (SS), nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Generally, hepatic SS is often self-limited; however 10%-30% of patients with hepatic SS progress to NASH. The cause(s) of the transition from SS to NASH are unclear. We aimed to test the contribution of nuclear erythroid 2-related factor 2 (Nrf2) on the progression of "benign" SS to NASH in mice fed a high fat diet. In doing so, we discovered the influence of fatty acid in that progression. METHOD: The involvement of Nrf2 in defending against the development of NASH was studied in an experimental model induced by a high-fat diet. Wild-type and Nrf2-null mice were fed the diet. Their specimens were analyzed for pathology as well as for fatty acid content and ratios. RESULT: In feeding the high-fat diet to the Wild-type and the Nrf2-null mice, the Wild-type mice increased hepatic fat deposition without inflammation or fibrosis (i.e., simple steatosis), while the Nrf2-null mice had significantly more hepatic steatosis and substantial inflammation, (i.e., nonalcoholic steatohepatitis). In addition, as a result of the high-fat diet, SFA (C20: 0, C22: 0) and MUFA (C18: 1, C20: 1) content in Nrf2-null mice were significantly higher than in Wild-type mice. In the Nrf2-null mice the PUFA/TFA ratio decreased; conversely, the MUFA/TFA ratio increased. CONCLUSION: The deletion of Nrf2 causes "benign" SS to develop into NASH in mice fed with a high-fat diet, through prompt fatty acid accumulation and disruption of hepatic fatty acid composition in the liver. SN - 1476-511X UR - https://www.unboundmedicine.com/medline/citation/24188280/Nrf2_deletion_causes_"benign"_simple_steatosis_to_develop_into_nonalcoholic_steatohepatitis_in_mice_fed_a_high_fat_diet_ L2 - https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-12-165 DB - PRIME DP - Unbound Medicine ER -