Regulation of FGF21 expression and secretion by retinoic acid receptor-related orphan receptor alpha

Yongjun Wang, Laura A Solt, Thomas P Burris
Journal of Biological Chemistry 2010 May 21, 285 (21): 15668-73
Fibroblast growth factor 21 (FGF21) is a hormone produced by fat and the liver that plays an important role in lipid metabolism. FGF21 expression is induced by peroxisome proliferator-actived receptor alpha in response to physiological conditions requiring increased fatty acid oxidation. Retinoic acid receptor-related receptor alpha (RORalpha) is another nuclear receptor that plays a critical role in lipid metabolism as well as in regulation of the circadian rhythm. In this study we demonstrate that RORalpha directly regulates the expression and secretion of FGF21. A canonical ROR response element was identified in the proximal promoter of the FGF21 gene and shown to exhibit functional activity. Overexpression of RORalpha in HepG2 cells resulted in increased expression and secretion of FGF21. Suppression of RORalpha expression caused a decrease in FGF21 expression and secretion, suggesting that RORalpha contributes to the basal expression of FGF21. These data suggest that one mechanism by which RORalpha regulates lipid metabolism may be by modulation of FGF21 secretion. Furthermore, this study identifies a clear link between RORalpha, a key regulator of the mammalian clock, and FGF21, an important hormone regulating glucose and lipid homeostasis.

Full Text Links

Find Full Text Links for this Article


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

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


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"