Résumé
This study was undertaken to test whether (i) the spontaneously hypertensive rat (SHR) heart displays lower exogenous long chain fatty acid (LCFA) utilization prior to hypertrophy and (ii) this is due to alterations in CD36 protein function. This was assessed in 7‐week‐old SHR and control Wistar rat hearts using ex vivo perfusions with 13C‐labeled substrates and various molecular biology techniques. Compared to controls, working hearts from young SHR display a lower contribution of exogenous LCFA to â‐oxidation (0.6‐fold) and triglycerides (2.8‐fold), which is not explained by transcriptional changes or malonyl‐CoA, a recognized â‐oxidation inhibitor. Other analyses demonstrate a lower CD36 protein membrane level (Western), but no change in its intracellular localization (confocal microscopy). While non‐synonymous mutations in SHR revealed by sequence alignment predicted an impact on CD36 post translational modifications (PTM), direct evidence support alterations in N‐glycosylation. Collectively, our results in the SHR heart highlight the crucial role of CD36 protein PTM in determining exogenous LCFA utilization. (Supported by the Fondation Bettencourt Schueller, FRSQ and CIHR).