title: Cardiospecific CD36 suppression by lentivirus-mediated RNA interference prevents cardiac hypertrophy and systolic dysfunction in high-fat-diet induced obese mice.
abstract: BACKGROUND
  Fatty acid (FA) catabolism abnormality has been proved to play an important role in obesity-related cardiomyopathy. We hypothesized that cardiospecific suppression of CD36, the predominant membrane FA transporter, would protect against obesity-related cardiomyopathy.
  
  
  METHODS
  Four-wk-old male C57BL/6 J mice were fed with either high-fat-diet (HFD) or control-normal-diet for 2 wk. Then they were subjected to intramyocardial injection with recombinant lentiviral vectors containing short hairpin RNAs to selectively downregulate the expression of either cardiac CD36 or irrelevant gene by RNA interference. After a 10-wk continuation of the diet, biochemical, functional, morphological, histological, metabolic and molecular profiles were assessed.
  
  
  RESULTS
  HFD administration elicited obesity, cardiac hypertrophy and systolic dysfunction accompanied with elevated serum levels of blood urea nitrogen (BUN), creatinine, fasting serum glucose (FSG), total cholesterol (TC) and triglyceride. Additionally, HFD consumption promoted lipid accumulation and reactive oxygen species (ROS) generation in the cardiomyocytes. Cardiospecific CD36 inhibition protected against HFD induced cardiac remodeling by decreasing heart/body weight ratio, increasing left ventricular (LV) ejection fraction and fractional shortening as well as normalizing LV diameter, without influencing body weight gain. Inhibition of cardiac CD36 also mitigated obesity induced alteration in BUN, creatinine and triglyceride, but had no effect on FSG or TC. Moreover, cardiospecific CD36 deficiency corrected myocardial lipid overaccumulation and intracellular ROS overproduction that were induced by HFD feeding.
  
  
  CONCLUSIONS
  Cardiospecific CD36 inhibition protects against the aggravation of cardiac functional and morphological changes associated with HFD induced obesity. CD36 represents a potential therapeutic target for obesity cardiomyopathy.
authors.affiliation: Department of Cardiology, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. zhangyijie@whu.edu.cn.|Cardiovascular Research Institute of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. zhangyijie@whu.edu.cn.|Central Laboratory of Renmin Hospital, Wuhan University, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. zhangyijie@whu.edu.cn.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. mbao@whu.edu.cn.|Cardiovascular Research Institute of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. mbao@whu.edu.cn.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Bao
authors.affiliation: Department of Cardiology, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. daimingyan@whu.edu.cn.|Cardiovascular Research Institute of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. daimingyan@whu.edu.cn.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Cardiology, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. wangxin-1985@163.com.|Cardiovascular Research Institute of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. wangxin-1985@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. hewenbo@whu.edu.cn.|Cardiovascular Research Institute of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. hewenbo@whu.edu.cn.
authors.forename: Wenbo
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Ultrasonography, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. 814056204@qq.com.
authors.forename: Tuantuan
authors.initials: T
authors.lastname: Tan
authors.affiliation: Department of Oncology, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. lindandan@whu.edu.cn.
authors.forename: Dandan
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Thoracic Surgery, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. wangwei1018@yeah.net.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. 375583680@qq.com.|Cardiovascular Research Institute of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. 375583680@qq.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Cardiovascular Research Institute of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. zhangrui050107@126.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001806:Blood Urea Nitrogen; D018955:CD36 Antigens / Q000235:genetics*; D006332:Cardiomegaly / Q000235:genetics* / Q000473:pathology; D009202:Cardiomyopathies / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D059305:Diet, High-Fat; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D016086:Lentivirus; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012709:Serum Albumin; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D018955:CD36 Antigens; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D014280:Triglycerides; D002784:Cholesterol; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase