Ceramide Mediates Vascular Dysfunction in Diet-Induced Obesity by PP2A-Mediated Dephosphorylation of the eNOS-Akt Complex
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Working model. HF feeding leads to arterial ceramide accumulation in vivo. Palmitate incubation elevates ceramide in isolated
arteries and endothelial cells in vitro. Ceramide increases the association of PP2A with eNOS and decreases the association
between eNOS and Akt and between eNOS and Hsp90. PP2A promotes the dephosphorylation of Akt that colocalizes with eNOS and/or
decreases eNOS phosphorylation at Ser1177 and Ser617 directly. This impairs NO bioavailability and leads to vascular dysfunction.