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

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 13C-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.

Research Highlights
► Alterations of CD36 in SHR are linked to reduced long chain fatty acid utilization.
► Post-translational modification of CD36 is crucial for its function.
► O-linked β-N-acetylglucosamine is involved in CD36 recruitment.
► N-glycosylation is a key process for CD36 function.