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Liver X receptor in cooperation with SREBP‐1c is a major lipid synthesis regulator in nonalcoholic fatty liver disease
Author(s) -
Higuchi Nobito,
Kato Masaki,
Shundo Yuki,
Tajiri Hirotaka,
Tanaka Masatake,
Yamashita Naoki,
Kohjima Motoyuki,
Kotoh Kazuhiro,
Nakamuta Makoto,
Takayanagi Ryoichi,
Enjoji Munechika
Publication year - 2008
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2008.00382.x
Subject(s) - carbohydrate responsive element binding protein , liver x receptor , sterol regulatory element binding protein , fatty acid synthase , medicine , nonalcoholic fatty liver disease , fatty liver , endocrinology , liver x receptor alpha , lipogenesis , lipid metabolism , biology , downregulation and upregulation , cholesterol , cancer research , transcription factor , sterol , nuclear receptor , biochemistry , gene , disease
Aim: Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver dysfunction and its incidence has increased markedly. However, the mechanisms involved in the pathogenesis of NAFLD in humans have not been thoroughly investigated. Sterol regulatory element binding protein (SREBP)‐1c and carbohydrate responsive element binding protein (ChREBP) are transcriptional factors that regulate the expression of lipogenic genes, including acetyl‐CoA carboxylases (ACCs) and fatty acid synthase (FAS). SREBP‐1c and ChREBP are transactivated by liver X receptor (LXR), a nuclear receptor that regulates the metabolism of cholesterol and fatty acids. To understand the mechanisms involved in the pathogenesis of NAFLD, we investigated the transcriptional factors and lipogenic genes activated in the liver with NAFLD. Methods: Real‐time PCR was carried out on liver biopsy samples from 20 NAFLD patients. The target genes studied were: ACC1, FAS, SREBP‐1c, ChREBP, AMP‐activated protein kinase (AMPK), and LXRα. Results: LXRα, SREBP‐1c, ACC1, and FAS were upregulated in NAFLD patients. Expression levels of LXR were four times greater than those of the controls and correlated significantly with SREBP‐1c, but not with ChREBP, levels. Conclusions: These findings suggest that LXR acts as one of the main regulators of lipid metabolism by regulating SREBP‐1c expression in NAFLD.