title: In Vitro and In Vivo Effects of Metformin on Osteopontin Expression in Mice Adipose-Derived Multipotent Stromal Cells and Adipose Tissue.
abstract: Metformin is applied not only as antidiabetic drug, but also in the treatment of obesity or as antiaging drug. The first part of the research discussed the effect of metformin at concentrations of 1 mM, 5 mM, and 10 mM on the morphology, ultrastructure, and proliferation potential of mice adipose-derived multipotent mesenchymal stromal cells (ASCs) in vitro. Additionally, we determined the influence of metformin on mice adipose tissue metabolism. This study has shown for the first time that metformin inhibits the proliferative potential of ASCs in vitro in a dose- and time-dependent manner. In addition, we have found a significant correlation between the activity of ASCs and osteopontin at the mRNA and protein level. Furthermore, we have demonstrated that 5 mM and 10 mM metformin have cytotoxic effect on ASCs, causing severe morphological, ultrastructural, and apoptotic changes. The reduced level of OPN in the adipose tissue of metformin-treated animals strongly correlated with the lower expression of Ki67 and CD105 and increased caspase-3. The metformin influenced also circulating levels of OPN, which is what was found with systemic and local action of metformin. The results are a valuable source of information regarding the in vitro effect of metformin on adipose-derived stem cells.
authors.affiliation: The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, Kozuchowska 5b Street, 50-631 Wroclaw, Poland ; Wrocławskie Centrum Badań EIT+, Stablowicka 147 Street, 54-066 Wroclaw, Poland.
authors.forename: Agnieszka
authors.identifier: 0000-0002-7314-9821
authors.initials: A
authors.lastname: Śmieszek
authors.affiliation: The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, Kozuchowska 5b Street, 50-631 Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Basińska
authors.affiliation: The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, Kozuchowska 5b Street, 50-631 Wroclaw, Poland.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Chrząstek
authors.affiliation: The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, Kozuchowska 5b Street, 50-631 Wroclaw, Poland ; Wrocławskie Centrum Badań EIT+, Stablowicka 147 Street, 54-066 Wroclaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Marycz
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D008687:Metformin / Q000008:administration & dosage*; D051379:Mice; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D053495:Osteopontin; D008687:Metformin