title: Modulation of glucose and lipid metabolism by porcine adiponectin receptor 1-transgenic mesenchymal stromal cells in diet-induced obese mice.
abstract: OBJECTIVE
  Obesity and its associated diseases demand better therapeutic strategies. Regenerative medicine combined with gene therapy has emerged as a promising approach in various clinical applications. Adiponectin (ApN) and its receptors have been demonstrated to play beneficial roles in modulating glucose and lipid homeostasis. In the current study, we tested such an approach by transplanting mesenchymal stromal cells (MSCs) from porcine ApN receptor (pAdipoR) 1-transgenic mice into high-fat/sucrose diet (HFSD)-fed mice.
  
  
  METHODS
  Twenty 6-week-old Friend virus B/NJNarl male mice were randomly assigned into four groups with the control fed a chow diet (chow) and others HFSD for 10 months. The HFSD groups were then intraperitoneally injected once per week for 8 weeks with placebo (200 μL phosphate-buffered saline), wild-type MSC (WT-MSC, 2 × 10(6) cells/200 μL phosphate-buffered saline) or pAdipoR1-transgenic MSC (pR1-tMSC, 2 × 10(6) cells/200 μL phosphate-buffered saline), respectively. Body weights, blood samples, tissue histology, and gene expression and protein levels of metabolism-associated genes were analyzed.
  
  
  RESULTS
  Both WT-MSC and pR1-tMSC transplantations restored the messenger RNA expression of AdipoR1, with those of glucose transporter 4 and 5'-adenosine monophosphate-activated protein kinase catalytic subunit α-1 and protein levels of pyruvate kinase induced by pR1-tMSC in the muscles of HFSD-fed mice. In the liver, both WT-MSC and pR1-tMSC ameliorated HFSD-induced hepatosteatosis, with the gene expression of lipoprotein lipase and hormone-sensitive lipase upregulated by the latter. Lastly, pR1-tMSC transplantation reduced fatty acid synthase mRNA levels in the adipose tissues of HFSD-fed mice.
  
  
  CONCLUSIONS
  This study demonstrates the modulatory actions of MSC and pR1-tMSC on genes associated with glucose and lipid metabolism and provides insights into its therapeutic application for obesity-associated metabolic complication.
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Yuan Yu
authors.initials: YY
authors.lastname: Lin
authors.forename: Ching Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Lin
authors.forename: Yao Pang
authors.initials: YP
authors.lastname: Chiu
authors.forename: Chih Chien
authors.initials: CC
authors.lastname: Chen
authors.forename: Bing Hsien
authors.initials: BH
authors.lastname: Liu
authors.forename: Harry John
authors.initials: HJ
authors.lastname: Mersmann
authors.forename: Shinn Chih
authors.initials: SC
authors.lastname: Wu
authors.forename: Shih Torng
authors.initials: ST
authors.lastname: Ding
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001786:Blood Glucose / Q000378:metabolism*; D064987:Cell- and Tissue-Based Therapy; D054890:Fatty Acid Synthase, Type I / Q000096:biosynthesis / Q000235:genetics; D015316:Genetic Therapy; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis; D022781:Hepatocytes / Q000378:metabolism; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000096:biosynthesis; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000628:therapy*; D011770:Pyruvate Kinase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D054419:Receptors, Adiponectin / Q000235:genetics*; D002787:Sterol Esterase / Q000378:metabolism; D013552:Swine
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D054890:Fatty Acid Synthase, Type I; D011770:Pyruvate Kinase; D002787:Sterol Esterase; D008071:Lipoprotein Lipase; D005947:Glucose
keywords: adiponectin receptor 1; diet-induced obesity; gene therapy; mesenchymal stromal cells