title: Adipose-derived mesenchymal stem cells improve glucose homeostasis in high-fat diet-induced obese mice.
abstract: BACKGROUND
  Effective therapies for obesity and diabetes are still lacking. The aim of this study was to evaluate whether a single intravenous infusion of syngeneic adipose-derived mesenchymal stem cells (ASCs) can reduce obesity, lower insulin resistance, and improve glucose homeostasis in a high-fat diet-induced obese (DIO) mouse model.
  
  
  METHODS
  Seven-week-old C57BL/6 mice were fed a high-fat diet for 20 weeks to generate the DIO mouse model. Mice were given a single intravenous infusion of ex vivo expanded syngeneic ASCs at 2 × 10(6) cells per mouse. DIO or CHOW mice injected with saline were used as controls. Body weights, blood glucose levels, glucose, and insulin tolerance test results were obtained before and 2 and 6 weeks after cell infusion. Triglyceride (TG), high-density lipoprotein (HDL), and insulin levels in serum were measured. Expressions of genes related to insulin resistance, including peroxisome proliferator-activated receptor γ (PPARγ) and insulin receptor (InsR), and inflammation (IL-6, F4/80, and nucleotide-binding oligomerization domain containing 2, or NOD2), were measured in livers at mRNA level by real-time-polymerase chain reaction analysis. Beta-cell mass in pancrheases from CHOW, DIO, and DIO + ASC mice was quantified. GFP(+) ASCs were injected, and the presence of GFP(+) cells in livers and pancreases was determined.
  
  
  RESULTS
  DIO mice that had received ASCs showed reduced body weights, reduced blood glucose levels, and increased glucose tolerance. ASC treatment was found to reduce TG levels and increase serum HDL levels. In livers, less fat cell deposition was observed, as were increased expression of InsR and PPARγ and reduction in expressions of IL-6 and F4/80. Treated mice showed well-preserved pancreatic β-cell mass with reduced expression of F4/80 and TNF-α compared with DIO controls. GFP(+) cells were found in liver and pancreas tissues at 1 and 2 weeks after cell injection.
  
  
  CONCLUSIONS
  ASC therapy is effective in lowering blood glucose levels and increasing glucose tolerance in DIO mice. The protective effects of ASCs arise at least in part from suppression of inflammation in the liver. In addition, ASCs are associated with better-preserved pancreatic β-cell mass.
authors.affiliation: Colleges of Life Sciences, Qingdao Agricultural University, 700 Chenyang Road, Chenyang, Shandong, 266109, P.R. China. caomingjun19881112@163.com.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Cao
authors.affiliation: College of Animal Science and Veterinary Medicine, 700 Chenyang Road, Chenyang, Shandong, 266109, P.R. China. qjpan@126.com.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Pan
authors.affiliation: College of Animal Science and Veterinary Medicine, 700 Chenyang Road, Chenyang, Shandong, 266109, P.R. China. donghuansheng@163.com.
authors.forename: Huansheng
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Pharmacology & Toxicology, Virginia Commonwealth University, 1 Hayden Dr., Petersburg, VA, 23806, USA. xyuan2@vcu.edu.
authors.forename: Xinxu
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Colleges of Life Sciences, Qingdao Agricultural University, 700 Chenyang Road, Chenyang, Shandong, 266109, P.R. China. liyang2951@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, Medical University of South Carolina, BSB 641, 173 Ashley Ave, Charleston, SC, 29425, USA. sunz@musc.edu.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Colleges of Life Sciences, Qingdao Agricultural University, 700 Chenyang Road, Chenyang, Shandong, 266109, P.R. China. 1163155358@qq.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Surgery, Medical University of South Carolina, BSB 641, 173 Ashley Ave, Charleston, SC, 29425, USA. wangho@musc.edu.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects*; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance; D006706:Homeostasis; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000628:therapy*; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D014280:Triglycerides; D005947:Glucose