Post-translational modifications, a key process in CD36 function: lessons from the spontaneously hypertensive rat heart.

Abstract CD36, a multifunctional protein, is involved in cardiac long chain fatty acid (LCFA) metabolism and in the etiology of heart diseases, yet the functional impact of Cd36 gene variants remains unclear. In 7-week-old spontaneously hypertensive rats (SHR), which, like humans, carry numerous mutations in Cd36 , we tested the hypothesis that their restricted cardiac LCFA utilization occurs prior to hypertrophy due to defective CD36 post-translational modifications (PTM), as assessed by ex vivo perfusion of 13 C-labeled substrates and biochemical techniques. Compared to their controls, SHR hearts displayed a lower (i) contribution of LCFA to β-oxidation (− 40%) and triglycerides (+ 2.8 folds), which was not explained by transcriptional changes or malonyl-CoA level, a recognized β-oxidation inhibitor, and (ii) membrane-associated CD36 protein level, but unchanged distribution. Other results demonstrate alterations in CD36 PTM in SHR hearts, specifically by N-glycosylation, and the importance of O-linked-β-N-acetylglucosamine for its membrane recruitment and role in LCFA use in the heart.