Demonstration of interaction of full‐length PPARα and LXRα

Abstract

The two ligand‐activated nuclear receptors: peroxisome proliferator activated receptor (PPAR) and liver‐X receptor (LXR) are known to play important roles in fatty acid (FA) metabolism. PPARα and LXRα are known to interact and function as heterodimeric partners; however, their specific activity is still unknown. Further, previous studies utilized either murine or truncated forms of these proteins, and whether full‐length PPARα and LXRα interact is unknown. Prior studies indicate that PPARα is activated by polyunsaturated fatty acids, saturated and/or unsaturated long chain fatty acyl‐CoA. However, not much is known about the effects of these ligands on the function or interaction of PPARα and LXRα. In the present study, the effects of FA and their CoA derivatives (FA‐CoA) on the interaction of full‐length human PPARα and LXRα were studied. Circular dichroic spectra of the two proteins in the presence or absence of FAs and their FA‐CoA were determined. Analyses showed that most FA do not significantly alter the structures, while FA‐CoA displayed structural changes indicating that the FA‐CoA affect PPARα and LXRα interaction. As high levels of FA are associated with certain metabolic disorders and also serve as natural ligands for PPARα, changes in structure and/or interaction between PPARα and LXRα may have significant effects on the normal functioning of a cell. This work was supported by USPHS NIH grant DK77573.