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Elovl6 promotes nonalcoholic steatohepatitis
Author(s) -
Matsuzaka Takashi,
Atsumi Ayaka,
Matsumori Rie,
Nie Tang,
Shinozaki Haruna,
SuzukiKemuriyama Noriko,
Kuba Motoko,
Nakagawa Yoshimi,
Ishii Kiyoaki,
Shimada Masako,
Kobayashi Kazuto,
Yatoh Shigeru,
Takahashi Akimitsu,
Takekoshi Kazuhiro,
Sone Hirohito,
Yahagi Naoya,
Suzuki Hiroaki,
Murata Soichiro,
Nakamuta Makoto,
Yamada Nobuhiro,
Shimano Hitoshi
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.25932
Subject(s) - steatohepatitis , insulin resistance , fatty liver , endocrinology , medicine , nonalcoholic fatty liver disease , biology , inflammasome , cirrhosis , obesity , inflammation , disease
Nonalcoholic steatohepatitis (NASH) is associated with obesity and type 2 diabetes, and an increased risk for liver cirrhosis and cancer. ELOVL family member 6, elongation of very long chain fatty acids (Elovl6), is a microsomal enzyme that regulates the elongation of C12‐16 saturated and monounsaturated fatty acids (FAs). We have shown previously that Elovl6 is a major target for sterol regulatory element binding proteins in the liver and that it plays a critical role in the development of obesity‐induced insulin resistance by modifying FA composition. To further investigate the role of Elovl6 in the development of NASH and its underlying mechanism, we used three independent mouse models with loss or gain of function of Elovl6, and human liver samples isolated from patients with NASH. Our results demonstrate that (1) Elovl6 is a critical modulator for atherogenic high‐fat diet–induced inflammation, oxidative stress, and fibrosis in the liver; (2) Elovl6 expression is positively correlated with severity of hepatosteatosis and liver injury in NASH patients; and (3) deletion of Elovl6 reduces palmitate‐induced activation of the NLR family pyrin domain‐containing 3 inflammasome; this could be at least one of the underlying mechanisms by which Elovl6 modulates the progress of NASH. Conclusion: Hepatic long‐chain fatty acid composition is a novel determinant in NASH development, and Elovl6 could be a potential therapeutic target for the prevention and treatment of NASH. (H EPATOLOGY 2012;56:2199–2208)