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标题:FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity.
时间:2019-11-19 22:40:21
DOI:10.1016/j.bbadis.2015.06.017
PMID:26111885
作者:Xiong, XiaoQing;Chen, Dan;Sun, HaiJian
出版源: Biochimica et biophysica acta
摘要:Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5), and contributes to the beneficial effects of exercise on metabolism. Here we report the therapeutical effects of FNDC5/irisin on metabolic derangements and insulin resistance in obesity, and show the lipolysis effect of irisin and its signal molecular mechanism. In obese mice, lentivirus mediated-FNDC5 overexpression enhanced energy expenditure, lipolysis and insulin sensitivity, and reduced hyperlipidemia, hyperglycemia, hyperinsulinism, blood pressure and norepinephrine levels; it increased hormone-sensitive lipase (HSL) expression and phosphorylation, and reduced perilipin level and adipocyte diameter in adipose tissues. Subcutaneous perfusion of irisin reduced hyperlipidemia and hyperglycemia, and improved insulin resistance. Either FNDC5 overexpression or irisin perfusion only induced a tendency toward a slight decrease in body weight in obese mice. In 3T3-L1 adipocytes, irisin enhanced basal lipolysis rather than isoproterenol-induced lipolysis, which were prevented by inhibition of adenylate cyclase or PKA; irisin increased the HSL and perilipin phosphorylation; it increased PKA activity, and cAMP and HSL mRNA levels, but reduced perilipin expression. These results indicate that FNDC5/irisin ameliorates glucose/lipid metabolic derangements and insulin resistance in obese mice, and enhances lipolysis via cAMP-PKA-HSL/perilipin pathway. FNDC5 or irisin can be taken as an effective therapeutic strategy for metabolic disorders
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目录:
  • FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity
    • 1. Introduction
    • 2. Materials and methods
      • 2.1. Mice and obesity model
      • 2.2. Cell culture
      • 2.3. Construction of FNDC5 expression plasmid
      • 2.4. Introduction of FNDC5 plasmid
      • 2.5. Subcutaneous perfusion of irisin
      • 2.6. Insulin and glucose tolerance tests
      • 2.7. Indirect calorimetry
      • 2.8. In vitro and in vivo lipolysis
      • 2.9. Quantitative RT-PCR analysis
      • 2.10. Western blot
      • 2.11. ELISA analysis
      • 2.12. Tissue embedding and H&E staining
      • 2.13. Chemicals
      • 2.14. Statistics
    • 3. Results
      • 3.1. Effectiveness of FNDC5 overexpression
      • 3.2. FNDC5 overexpression increases energy expenditure
      • 3.3. FNDC5 overexpression improves lipid metabolism
      • 3.4. FNDC5 overexpression improves glucose metabolism and insulin resistance
      • 3.5. FNDC5 overexpression reduces blood pressure
      • 3.6. FNDC5 overexpression increases UCP1 expression
      • 3.7. FNDC5 overexpression promotes lipolysis and reduces the size of adipocytes in SAT
      • 3.8. FNDC5 overexpression enhanced lipolysis via cAMP–PKA–perilipin/HSL pathway
      • 3.9. Persistent perfusion of irisin improves lipid metabolism and insulin resistance
      • 3.10. Irisin enhances lipolysis via cAMP–PKA–HSL/perilipin pathway in vitro
      • 3.11. Irisin enhances UCP1 mRNA and Akt phosphorylation in vitro
    • 4. Discussion
    • 5. Conclusion
    • Transparency document
    • Conflict of interest
    • Acknowledgments
    • Appendix A. Supplementary data
    • References

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