title: Cluster Differentiating 36 (CD36) Deficiency Attenuates Obesity-Associated Oxidative Stress in the Heart.
abstract: Obesity is often associated with a state of oxidative stress and increased lipid deposition in the heart. More importantly, obesity increases lipid influx into the heart and induces excessive production of reactive oxygen species (ROS) leading to cell toxicity and metabolic dysfunction. Cluster differentiating 36 (CD36) protein is highly expressed in the heart and regulates lipid utilization but its role in obesity-associated oxidative stress is still not clear.
  
  
  
  The aim of this study was to determine the impact of CD36 deficiency on cardiac steatosis, oxidative stress and lipotoxicity associated with obesity.
  
  
  
  Studies were conducted in control (Lean), obese leptin-deficient (Lepob/ob) and leptin-CD36 double null (Lepob/obCD36-/-) mice. Compared to lean mice, cardiac steatosis, and fatty acid (FA) uptake and oxidation were increased in Lepob/ob mice, while glucose uptake and oxidation was reduced. Moreover, insulin resistance, oxidative stress markers and NADPH oxidase-dependent ROS production were markedly enhanced. This was associated with the induction of NADPH oxidase expression, and increased membrane-associated p47phox, p67phox and protein kinase C. Silencing CD36 in Lepob/ob mice prevented cardiac steatosis, increased insulin sensitivity and glucose utilization, but reduced FA uptake and oxidation. Moreover, CD36 deficiency reduced NADPH oxidase activity and decreased NADPH oxidase-dependent ROS production. In isolated cardiomyocytes, CD36 deficiency reduced palmitate-induced ROS production and normalized NADPH oxidase activity.
  
  
  
  CD36 deficiency prevented obesity-associated cardiac steatosis and insulin resistance, and reduced NADPH oxidase-dependent ROS production. The study demonstrates that CD36 regulates NADPH oxidase activity and mediates FA-induced oxidative stress.
authors.affiliation: Department of Surgery, Hackensack University Medical Center, New Jersey 07601, United States of America.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Gharib
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, Tennessee 37212, United States of America.
authors.forename: Huan
authors.initials: H
authors.lastname: Tao
authors.affiliation: Nutritional Sciences, Howard University, Washington DC 20059, United States of America.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Fungwe
authors.affiliation: Department of Surgery, Hackensack University Medical Center, New Jersey 07601, United States of America.
authors.forename: Tahar
authors.initials: T
authors.lastname: Hajri
mesh_terms: D000818:Animals; D001791:Blood Platelet Disorders / Q000235:genetics*; D001835:Body Weight; D018955:CD36 Antigens / Q000172:deficiency*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D005951:Glucose Tolerance Test; D006321:Heart / Q000503:physiopathology*; D006579:Heterozygote; D006720:Homozygote; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008861:Microsomes / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology; D019255:NADPH Oxidases / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000235:genetics; D009929:Organ Size; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010168:Palmitates / Q000378:metabolism; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D005227:Fatty Acids; D007328:Insulin; D020738:Leptin; D010168:Palmitates; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D010100:Oxygen