CD36 Deficiency Reduces Obesity‐Associated Inflammation and Oxidative Stress in Heart

Abstract

Mounting evidence shows that obesity and diabetes are associated with structural and functional changes in the heart. CD36 protein is highly expressed in heart and regulates lipid utilization in cardiac myocytes. In this study, we investigate the impact of CD36 expression in obesity‐associated inflammation in heart. 
 Studies were conducted in control lean, obese leptin deficient (LepOb/Ob) and leptin deficient‐CD36 null (LepOb/Ob CD36‐/‐) mice. Histology and immunohistochemisty were conducted to examine heart structure and presence of macrophages. Uptake and oxidation glucose and fatty acids was tested in primary cultures of ventricular myocytes. Finally, the effects of fatty acid treatment on oxidative stress and activity of pro‐inflammatory kinases were examined in isolated cardiac myocytes. In LepOb/Ob, glucose uptake and oxidation in heart was lower than normal weight mice, while cardiac FA oxidation was strongly higher than normal. Silencing CD36 markedly improved insulin sensitivity and glucose uptake in heart, but marked reduced FA oxidation. Moreover, CD36 deficiency reduced macrophage content, oxidative stress markers and expression of pro‐inflammatory cytokines in heart. Chronic treatment with palmitate strongly induced oxidative stress and inflammatory markers in LepOb/Ob cardiac myocytes, but was clearly less effective in LepOb/Ob‐CD36‐/‐ cardiacmyocytes. 
 These results show that CD36 deficiency induces a significant reduction of obesity‐associated oxidative stress and inflammation in heart, in parallel to a drop of lipid infiltration and improved insulin sensitivity