1. Transplantation of neuregulin 4-overexpressing adipose-derived mesenchymal stem cells ameliorates insulin resistance by attenuating hepatic steatosis.
- Author
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Wang W, Zhang Y, Yang C, Wang Y, Shen J, Shi M, and Wang B
- Subjects
- Adipose Tissue cytology, Adipose Tissue metabolism, Animals, Cells, Cultured, Cholesterol metabolism, Glucose Transporter Type 4 metabolism, Lipogenesis, Liver metabolism, Male, Mesenchymal Stem Cells cytology, Mice, Mice, Inbred C57BL, Neuregulins metabolism, Sterol Regulatory Element Binding Protein 1 metabolism, Triglycerides metabolism, Tumor Necrosis Factor-alpha metabolism, Fatty Liver therapy, Genetic Therapy methods, Insulin Resistance, Mesenchymal Stem Cell Transplantation methods, Mesenchymal Stem Cells metabolism, Neuregulins genetics
- Abstract
Impact Statement: Due to high-fat and high-sugar diets accompanied by sedentary lifestyles, diabetes has become a global epidemic. Literature findings suggest a potential therapeutic effect of Nrg4 on treating obesity-related metabolic disorders including type 2 diabetes (T2D). Adipose tissue-derived MSCs (ADSCs) were used in our study as they are abundant and can be harvested with minimally invasive procedures. In the end, our study reveals that ADSC transplantation improves glucose tolerance and metabolic balance in HFD-fed mice by multiple mechanisms, including upregulating GLUT4 expression and suppressing inflammation. More importantly, our study shows that Nrg4 overexpression could improve the efficacy of ADSCs in ameliorating insulin resistance (IR) and other obesity-related metabolic disorders, given the function of Nrg4 in attenuating hepatic lipogenesis. It would provide a new therapeutic strategy for the treatment of obesity, IR, and T2D.
- Published
- 2019
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