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Sci Rep. 2015 Dec 1;5:17604. doi: 10.1038/srep17604.

Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a lithogenic diet-fed Ldlr(-/-) mouse model.

Author information

1
Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
2
Laboratory of Proteomics and Biomolecular Science, Biomedical Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
3
Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
4
Department of Internal Medicine, Faculty of Medicine, Niigata University, 1-754 Asahimachi, Niigata 951-8510, Japan.
5
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.

Abstract

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can develop into liver cirrhosis and cancer. Elongation of very long chain fatty acids (ELOVL) family member 6 (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids (FAs). We have previously shown that Elovl6 plays an important role in the development of hepatic insulin resistance and NASH by modifying FA composition. Recent studies have linked altered hepatic cholesterol homeostasis and cholesterol accumulation to the pathogenesis of NASH. In the present study, we further investigated the role of Elovl6 in the progression of lithogenic diet (LD)-induced steatohepatitis. We showed that the absence of Elovl6 suppresses hepatic lipid accumulation, plasma total cholesterol and total bile acid (BA) levels in LDL receptor-deficient (Ldlr(-/-)) mice challenged with a LD. The absence of Elovl6 also decreases hepatic inflammation, oxidative stress and liver injury, but increases the formation of cholesterol crystals in the less dilated gallbladder. These findings suggest that Elovl6-mediated changes in hepatic FA composition, especially oleic acid (C18:1n-9), control handling of hepatic cholesterol and BA, which protects against hepatotoxicity and steatohepatitis, but promotes gallstone formation in LD-fed Ldlr(-/-) mice.

PMID:
26619823
PMCID:
PMC4664962
DOI:
10.1038/srep17604
[Indexed for MEDLINE]
Free PMC Article

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