Niche-dependent regulations of metabolic balance in high-fat diet-induced diabetic mice by mesenchymal stromal cells

Andrea T ung Qian Ji, Yun Chuang Chang, Yun Ju Fu, Oscar K. Lee, Jennifer H. Ho

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Mesenchymal stromal cells (MSCs) have great potential to maintain glucose homeostasis and metabolic balance. Here, we demonstrate that in mice continuously fed with high-fat diet (HFD) that developed non-insulin-dependent diabetes, two episodes of systemic MSC transplantations effectively improve glucose tolerance and blood glucose homeostasis and reduce body weight through targeting pancreas and insulin-sensitive tissues and organs via site-specific mechanisms. MSCs support pancreatic islet growth by direct differentiation into insulin-producing cells and by mitigating the cytotoxicity of interleukin 1 (IL-1) and tumor necrosis factor-α (TNF-α) in the pancreas. Localization of MSCs in the liver and skeletal muscles in diabetic animals is also enhanced and therefore improves glucose tolerance, although long-term engraftment is not observed. MSCs prevent HFD-induced fatty liver development and restore glycogen storage in hepatocytes. Increased expression of IL-1 receptor antagonist and Glut4 in skeletal muscles after MSC transplantation results in better blood glucose homeostasis. Intriguingly, systemic MSC transplantation does not alter adipocyte number, but it decreases HFD-induced cell infiltration in adipose tissues and reduces serum levels of adipokines, including leptin and TNF-α. Taken together, systemic MSC transplantation ameliorates HFD-induced obesity and restores metabolic balance through multisystemic regulations that are niche dependent. Such findings have supported systemic transplantation of MSCs to correct metabolic imbalance.

Original languageEnglish
Pages (from-to)926-936
Number of pages11
JournalDiabetes
Volume64
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

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High Fat Diet
Mesenchymal Stromal Cells
Cell Transplantation
Homeostasis
Glucose
Blood Glucose
Pancreas
Skeletal Muscle
Tumor Necrosis Factor-alpha
Insulin
Adipokines
Interleukin-1 Receptors
Fatty Liver
Leptin
Glycogen
Interleukin-1
Islets of Langerhans
Adipocytes
Adipose Tissue
Hepatocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Niche-dependent regulations of metabolic balance in high-fat diet-induced diabetic mice by mesenchymal stromal cells. / Ji, Andrea T ung Qian; Chang, Yun Chuang; Fu, Yun Ju; Lee, Oscar K.; Ho, Jennifer H.

In: Diabetes, Vol. 64, No. 3, 01.03.2015, p. 926-936.

Research output: Contribution to journalArticle

Ji, Andrea T ung Qian ; Chang, Yun Chuang ; Fu, Yun Ju ; Lee, Oscar K. ; Ho, Jennifer H. / Niche-dependent regulations of metabolic balance in high-fat diet-induced diabetic mice by mesenchymal stromal cells. In: Diabetes. 2015 ; Vol. 64, No. 3. pp. 926-936.
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