Activation of the PPARγ-LXRα-ABC transcriptional cascade by ghrelin is dependent on the PI3-K/Akt pathway.

<p>(<b>A</b>) Role of the PI3-K pathway on gene expression analysis from THP-1 cells treated with 100 nM ghrelin and 5 nM LY294002 for 48 h. Representative images and fold changes of mRNA expression are shown for the indicated genes. (<b>B</b>) Immunoblot analysis of THP-1 cells treated with ghrelin in presence or absence of 5 nM LY294002 for 48 h. Fold changes are shown relative to untreated cells. (<b>C</b>) A proposed model for the GHS-R1a-induced signaling to PPARγ in macrophages. Activation of GHS-R1a by ghrelin promotes the recruitment and activation of a Fyn/Dok-1 complex with the subsequent decrease in Erk1/2-mediated phosphorylation of PPARγ Ser-84, restraining its inhibitory potential. Ghrelin also activates the PI3-K/Akt pathway through a Gα_q–dependent mechanism, which then promotes PPARγ AF-1 phosphorylation independently of Ser-84, resulting in receptor transcriptional activation and increase in the PPARγ-LXRα-ABCA1/G1 metabolic cascade in macrophages.