Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: role of PPARalpha, PPARgamma and LXRalpha.

ABSTRACT: Disruption of lipid and carbohydrate homeostasis is an important factor in the development of prevalent metabolic diseases such as diabetes, obesity, and atherosclerosis. Therefore, small molecules that could reduce insulin dependence and regulate dyslipidemia could have a dramatic effect on public health. The grapefruit flavonoid naringenin has been shown to normalize lipids in diabetes and hypercholesterolemia, as well as inhibit the production of HCV. Here, we demonstrate that naringenin regulates the activity of nuclear receptors PPARalpha, PPARgamma, and LXRalpha. We show it activates the ligand-binding domain of both PPARalpha and PPARgamma, while inhibiting LXRalpha in GAL4-fusion reporters. Using TR-FRET, we show that naringenin is a partial agonist of LXRalpha, inhibiting its asso

SUBMITTER: Goldwasser J 

PROVIDER: S-EPMC2928300 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature