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Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation

  • Authors:
    • Cui Chen
    • Zheying Meng
    • Yuanyi Zheng
    • Bing Hu
    • E. Shen
  • View Affiliations / Copyright

    Affiliations: Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 75-84
    |
    Published online on: October 25, 2017
       https://doi.org/10.3892/etm.2017.5375
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Abstract

Diabetic cardiomyopathy (DCM) is one of the major causes of morbidity and mortality in diabetic patients. Recent studies have demonstrated an increased level of fibroblast growth factor 21 (FGF21) in the plasma of DCM patients, and FGF21 has been proven to be a cardiovascular protector of the heart. The present study aimed to further investigate the pathogenic role of FGF21 in DCM, hypothesizing that a lack of FGF21 may promote the progression of DCM by regulating the lipid metabolism, cardiac hypertrophy and cardiac fibrosis, thus deteriorating the cardiac dysfunction. A total of 44 mice were randomly assigned into the normal (n=6), DCM (n=6), normal + scrambled siRNA (n=6), DCM + scrambled siRNA (n=6), normal + FGF21 siRNA (n=10) and DCM + FGF21 siRNA (n=10) groups. Type 1 diabetes mellitus was induced to mice in the DCM groups by streptozotocin injection, while FGF21 expression was inhibited by FGF21 siRNA. Normal and DCM mice administrated with scrambled siRNA were respectively regarded as the controls for the normal + FGF21 siRNA and DCM + FGF21 siRNA groups. In the DCM group, FGF21 inhibition promoted cardiac hypertrophy and fibrosis, and the expression levels of their indicators, including atrial natriuretic factor, α‑skeletal actin, collagen type I and III, and transforming growth factor‑β, increased, leading to further decreased cardiac function. In addition, FGF21 inhibition in DCM mice elevated the quantity of lipid droplets and the concentration of heart triglycerides, plasma triglycerides and cholesterol levels, accompanied by downregulation of peroxisome proliferator‑activated receptor γ co‑activator 1α (PGC‑1α) and upregulation of cluster of differentiation (CD)36. Thus, the results indicated that FGF21 inhibition exacerbates the cardiac dysfunction by aggravating the lipid accumulation through regulating the expression levels of PGC‑1α and CD36. In conclusion, it is suggested that FGF21 may be a potentially useful agent in the treatment of DCM.
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Copy and paste a formatted citation
Spandidos Publications style
Chen C, Meng Z, Zheng Y, Hu B and Shen E: Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation. Exp Ther Med 15: 75-84, 2018.
APA
Chen, C., Meng, Z., Zheng, Y., Hu, B., & Shen, E. (2018). Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation. Experimental and Therapeutic Medicine, 15, 75-84. https://doi.org/10.3892/etm.2017.5375
MLA
Chen, C., Meng, Z., Zheng, Y., Hu, B., Shen, E."Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation". Experimental and Therapeutic Medicine 15.1 (2018): 75-84.
Chicago
Chen, C., Meng, Z., Zheng, Y., Hu, B., Shen, E."Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation". Experimental and Therapeutic Medicine 15, no. 1 (2018): 75-84. https://doi.org/10.3892/etm.2017.5375
Copy and paste a formatted citation
x
Spandidos Publications style
Chen C, Meng Z, Zheng Y, Hu B and Shen E: Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation. Exp Ther Med 15: 75-84, 2018.
APA
Chen, C., Meng, Z., Zheng, Y., Hu, B., & Shen, E. (2018). Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation. Experimental and Therapeutic Medicine, 15, 75-84. https://doi.org/10.3892/etm.2017.5375
MLA
Chen, C., Meng, Z., Zheng, Y., Hu, B., Shen, E."Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation". Experimental and Therapeutic Medicine 15.1 (2018): 75-84.
Chicago
Chen, C., Meng, Z., Zheng, Y., Hu, B., Shen, E."Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation". Experimental and Therapeutic Medicine 15, no. 1 (2018): 75-84. https://doi.org/10.3892/etm.2017.5375
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