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 journalArticlepeer-review

27 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

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Niche-dependent regulations of metabolic balance in high-fat diet-induced diabetic mice by mesenchymal stromal cells'. Together they form a unique fingerprint.

Cite this