title: GH action influences adipogenesis of mouse adipose tissue-derived mesenchymal stem cells.
abstract: GH influences adipocyte differentiation, but both stimulatory and inhibitory effects have been described. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are multipotent and are able to differentiate into adipocytes, among other cells. Canonical Wnt/β-catenin signaling activation impairs adipogenesis. The aim of the present study was to elucidate the role of GH on AT-MSC adipogenesis using cells isolated from male GH receptor knockout (GHRKO), bovine GH transgenic (bGH) mice, and wild-type littermate control (WT) mice. AT-MSCs from subcutaneous (sc), epididiymal (epi), and mesenteric (mes) AT depots were identified and isolated by flow cytometry (Pdgfrα+ Sca1+ Cd45- Ter119- cells). Their in vitro adipogenic differentiation capacity was determined by cell morphology and real-time RT-PCR. Using identical in vitro conditions, adipogenic differentiation of AT-MSCs was only achieved in the sc depot, and not in epi and mes depots. Notably, we observed an increased differentiation in cells isolated from sc-GHRKO and an impaired differentiation of sc-bGH cells as compared to sc-WT cells. Axin2, a marker of Wnt/β-catenin activation, was increased in mature sc-bGH adipocytes, which suggests that activation of this pathway may be responsible for the decreased adipogenesis. Thus, the present study demonstrates that (i) adipose tissue in mice has a well-defined population of Pdgfrα+ Sca1+ MSCs; (ii) the differentiation capacity of AT-MSCs varies from depot to depot regardless of GH genotype; (iii) the lack of GH action increases adipogenesis in the sc depot; and iv) activation of the Wnt/β-catenin pathway might mediate the GH effect on AT-MSCs. Taken together, the present results suggest that GH diminishes fat mass in part by altering adipogenesis of MSCs.
authors.affiliation: Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA nicola@ous-hf.no.
authors.forename: Nicoleta C
authors.initials: NC
authors.lastname: Olarescu
authors.affiliation: Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA.
authors.forename: Darlene E
authors.initials: DE
authors.lastname: Berryman
authors.affiliation: Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Householder
authors.affiliation: Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA.
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Lubbers
authors.affiliation: Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA.
authors.forename: Edward O
authors.initials: EO
authors.lastname: List
authors.affiliation: Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA.
authors.forename: Fabian
authors.initials: F
authors.lastname: Benencia
authors.affiliation: Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.affiliation: Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA Section of Specialized EndocrinologyDepartment of Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950, N-0424 Oslo, NorwayFaculty of MedicineUniversity of Oslo, Oslo, NorwayEdison Biotechnology InstituteOhio University, Athens, Ohio, USAHeritage College of Osteopathic MedicineOhio University, Athens, Ohio, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Bollerslev
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000502:physiology*; D052436:Adipose Tissue, White / Q000166:cytology*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation; D013006:Growth Hormone / Q000235:genetics / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; C495267:CTNNB1 protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D051176:beta Catenin; C073294:growth hormone, bovine; D013006:Growth Hormone; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: Wnt/β-catenin signaling; adipogenesis; adipose tissue-derived mesenchymal stem cells; growth hormone