Overexpressing the novel autocrine/endocrine adipokine WISP2 induces hyperplasia of the heart, white and brown adipose tissues and prevents insulin resistance
Grünberg, John R. (Sahlgrenska Academy at the University of Gothenburg. The Lundberg Laboratory for Diabetes Research)
Hoffmann, Jenny M. (Sahlgrenska Academy at the University of Gothenburg. The Lundberg Laboratory for Diabetes Research)
Hedjazifar, Shahram (Sahlgrenska Academy at the University of Gothenburg. The Lundberg Laboratory for Diabetes Research)
Nerstedt, Annika (Sahlgrenska Academy at the University of Gothenburg. The Lundberg Laboratory for Diabetes Research)
Jenndahl, Lachmi (Sahlgrenska Academy at the University of Gothenburg. The Lundberg Laboratory for Diabetes Research)
Elvin, Johannes (Sahlgrenska Academy at the University of Gothenburg. The Lundberg Laboratory for Diabetes Research)
Castellot, John (Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine)
Wei, Lan (Massachusetts General Hospital (Boston))
Movérare-Skrtic, Sofia (Sahlgrenska Academy at the University of Gothenburg. Centre for Bone and Arthritis Research)
Ohlsson, Claes (Sahlgrenska Academy at the University of Gothenburg. Centre for Bone and Arthritis Research)
Holm, Louise Mannerås (Sahlgrenska Academy at the University of Gothenburg. The Wallenberg Laboratory)
Bäckhed, Fredrik (University of Copenhagen. Novo Nordisk Foundation Center for Basic Metabolic Research)
Syed, Ismail (Beth Israel Deaconess and Harvard Medical School)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Centre de Biotecnologia Animal i de Teràpia Gènica (CBATEG))
Saghatelian, Alan (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica))
Kahn, Barbara B. (Beth Israel Deaconess and Harvard Medical School)
Hammarstedt, Ann (Sahlgrenska Academy at the University of Gothenburg. The Lundberg Laboratory for Diabetes Research)
Smith, Ulf (Sahlgrenska Academy at the University of Gothenburg. The Lundberg Laboratory for Diabetes Research)

Date:	2017
Abstract:	WISP2 is a novel adipokine, most highly expressed in the adipose tissue and primarily in undifferentiated mesenchymal cells. As a secreted protein, it is an autocrine/paracrine activator of canonical WNT signaling and, as an intracellular protein, it helps to maintain precursor cells undifferentiated. To examine effects of increased WISP2 in vivo, we generated an aP2-WISP2 transgenic (Tg) mouse. These mice had increased serum levels of WISP2, increased lean body mass and whole body energy expenditure, hyperplastic brown/white adipose tissues and larger hyperplastic hearts. Obese Tg mice remained insulin sensitive, had increased glucose uptake by adipose cells and skeletal muscle in vivo and ex vivo, increased GLUT4, increased ChREBP and markers of adipose tissue lipogenesis. Serum levels of the novel fatty acid esters of hydroxy fatty acids (FAHFAs) were increased and transplantation of Tg adipose tissue improved glucose tolerance in recipient mice supporting a role of secreted FAHFAs. The growth-promoting effect of WISP2 was shown by increased BrdU incorporation in vivo and Tg serum increased mesenchymal precursor cell proliferation in vitro. In contrast to conventional canonical WNT ligands, WISP2 expression was inhibited by BMP4 thereby allowing normal induction of adipogenesis. WISP2 is a novel secreted regulator of mesenchymal tissue cellularity.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 7 (02 2017) , ISSN 2045-2322

DOI: 10.1038/srep43515
PMID: 28240264

15 p, 2.8 MB

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