OPEN IN READ APP
JOURNAL ARTICLE

Liver X receptor negatively regulates fibroblast growth factor 21 in the fatty liver induced by cholesterol-enriched diet

Takashi Uebanso, Yutaka Taketani, Hironori Yamamoto, Kikuko Amo, Sarasa Tanaka, Hidekazu Arai, Yuichiro Takei, Masashi Masuda, Hisami Yamanaka-Okumura, Eiji Takeda
Journal of Nutritional Biochemistry 2012, 23 (7): 785-90
21889884
Cholesterol homeostasis is regulated by the liver X receptor (LXR) at the transcriptional level, but it remains unknown whether LXR can affect expression levels of intrahepatic lipolysis related gene. Recent evidence has demonstrated that fibroblast growth factor 21 (FGF21) regulates hepatic lipolysis and fatty acid utilization. In the present study, we examined the role of LXR in FGF21 gene expression associated with regulation of cross-talk signals between cholesterol and triglyceride metabolism in the liver. An in vivo cholesterol feeding test revealed that intake of excess cholesterol increased cholesterol catabolism related gene expression as well as fatty-acid biosynthesis related gene expression. Moreover, the accumulated cholesterol suppressed FGF21 and hormone-sensitive lipase (HSL) gene expression. After 15-day cholesterol feeding, hepatic triglyceride concentrations were negatively correlated with expression levels of the FGF21 and HSL genes in the liver. An LXR agonist (TO-901317) repressed the FGF21 gene expression in mouse primary hepatocytes and HepG2 cells. A promoter deletion study and electrophoretic mobility shift assay revealed that the human FGF21 promoter has at least one LXR response element located from -37 to -22 bp. In summary, LXR represses FGF21 gene expression at the transcription level and might suppress lipolysis and lipid utilization to protect the liver from excess accumulation of toxic cholesterol.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
21889884
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"