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Cardiospecific CD36 suppression by lentivirus-mediated RNA interference prevents cardiac hypertrophy and systolic dysfunction in high-fat-diet induced obese mice.

Zhang Y, Bao M, Dai M, Wang X, He W, Tan T, Lin D, Wang W, Wen Y, Zhang R - Cardiovasc Diabetol (2015)

Bottom Line: 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.Cardiospecific CD36 inhibition protects against the aggravation of cardiac functional and morphological changes associated with HFD induced obesity.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. zhangyijie@whu.edu.cn.

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.

No MeSH data available.


Related in: MedlinePlus

Phenotype of heart. a Gross appearance of a representative heart from each group. HFD induced visually cardiac hypertrophy compared to CND. Excised hearts were arrested in diastole with 10 % KCl. b Gross heart weight and heart/BW ratio revealed significant increase with HFD compared to CND. Cardiospecific CD36 inhibition significantly decreased heart/BW ratio. BW: body weight. Values are mean ± SD, N = 8 for each group. a, vs. N-mock; b, vs. N-CD36; c, vs. O-mock; (*) P < 0.05
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Fig3: Phenotype of heart. a Gross appearance of a representative heart from each group. HFD induced visually cardiac hypertrophy compared to CND. Excised hearts were arrested in diastole with 10 % KCl. b Gross heart weight and heart/BW ratio revealed significant increase with HFD compared to CND. Cardiospecific CD36 inhibition significantly decreased heart/BW ratio. BW: body weight. Values are mean ± SD, N = 8 for each group. a, vs. N-mock; b, vs. N-CD36; c, vs. O-mock; (*) P < 0.05

Mentions: Obesity cardiomyopathy is characterized by cardiac hypertrophy, a phenotype that is commonly observed in both obese humans and animals [4, 29]. To investigate the effects of CD36 deficiency on cardiac hypertrophy, the hearts were excised and weighted. The heart weight of 16-wk-old O-mock mice was significantly higher than that of N-mock mice. Cardiac CD36 suppression in O-CD36 mice significantly reduced heart weight but not back to normal level (Fig. 3). Heart/body weight ratio (heart/BW ratio) was calculated in this study to normalize weights and eliminate confounding effects of differences in size. As shown in Fig. 3b, HFD feeding caused a significant increase in heart/BW ratio in O-mock mice compared to N-mock and N-CD36 mice. Surprisingly, cardiac CD36 RNAi completely normalized heart/BW ratio back to normal level.Fig. 3


Cardiospecific CD36 suppression by lentivirus-mediated RNA interference prevents cardiac hypertrophy and systolic dysfunction in high-fat-diet induced obese mice.

Zhang Y, Bao M, Dai M, Wang X, He W, Tan T, Lin D, Wang W, Wen Y, Zhang R - Cardiovasc Diabetol (2015)

Phenotype of heart. a Gross appearance of a representative heart from each group. HFD induced visually cardiac hypertrophy compared to CND. Excised hearts were arrested in diastole with 10 % KCl. b Gross heart weight and heart/BW ratio revealed significant increase with HFD compared to CND. Cardiospecific CD36 inhibition significantly decreased heart/BW ratio. BW: body weight. Values are mean ± SD, N = 8 for each group. a, vs. N-mock; b, vs. N-CD36; c, vs. O-mock; (*) P < 0.05
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4464858&req=5

Fig3: Phenotype of heart. a Gross appearance of a representative heart from each group. HFD induced visually cardiac hypertrophy compared to CND. Excised hearts were arrested in diastole with 10 % KCl. b Gross heart weight and heart/BW ratio revealed significant increase with HFD compared to CND. Cardiospecific CD36 inhibition significantly decreased heart/BW ratio. BW: body weight. Values are mean ± SD, N = 8 for each group. a, vs. N-mock; b, vs. N-CD36; c, vs. O-mock; (*) P < 0.05
Mentions: Obesity cardiomyopathy is characterized by cardiac hypertrophy, a phenotype that is commonly observed in both obese humans and animals [4, 29]. To investigate the effects of CD36 deficiency on cardiac hypertrophy, the hearts were excised and weighted. The heart weight of 16-wk-old O-mock mice was significantly higher than that of N-mock mice. Cardiac CD36 suppression in O-CD36 mice significantly reduced heart weight but not back to normal level (Fig. 3). Heart/body weight ratio (heart/BW ratio) was calculated in this study to normalize weights and eliminate confounding effects of differences in size. As shown in Fig. 3b, HFD feeding caused a significant increase in heart/BW ratio in O-mock mice compared to N-mock and N-CD36 mice. Surprisingly, cardiac CD36 RNAi completely normalized heart/BW ratio back to normal level.Fig. 3

Bottom Line: 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.Cardiospecific CD36 inhibition protects against the aggravation of cardiac functional and morphological changes associated with HFD induced obesity.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuhan, 430060, Peoples Republic of China. zhangyijie@whu.edu.cn.

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.

No MeSH data available.


Related in: MedlinePlus