Overexpressing the novel autocrine/endocrine adipokine WISP2 induces hyperplasia of the heart, white and brown adipose tissues and prevents insulin resistance
Autor: | Alan Saghatelian, John J. Castellot, Johannes Elvin, Barbara B. Kahn, Lan Wei, Ann Hammarstedt, Claes Ohlsson, Sofia Movérare-Skrtic, Fredrik Bäckhed, Shahram Hedjazifar, Annika Nerstedt, Louise Mannerås Holm, Ismail Syed, Fatima Bosch, Jenny M. Hoffmann, John R. Grünberg, Ulf Smith, Lachmi Jenndahl |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Glucose uptake Adipose tissue Gene Expression Cell Count Bone Morphogenetic Protein 4 Mice 0302 clinical medicine Adipose Tissue Brown Transforming Growth Factor beta Insulin Multidisciplinary Glucose Transporter Type 4 Intracellular Signaling Peptides and Proteins Autocrine Communication Adipose Tissue Adipogenesis Lipogenesis Body Composition medicine.medical_specialty Genotype Adipose Tissue White Adipokine 030209 endocrinology & metabolism Mice Transgenic Biology Article 03 medical and health sciences Paracrine signalling Internal medicine medicine Journal Article Animals Autocrine signalling Cell Proliferation Cell Size Hyperplasia Myocardium Body Weight Mesenchymal Stem Cells Glucose Tolerance Test 030104 developmental biology Endocrinology Glucose biology.protein Insulin Resistance Energy Metabolism GLUT4 Biomarkers |
Zdroj: | Scientific Reports Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Grünberg, J R, Hoffmann, J M, Hedjazifar, S, Nerstedt, A, Jenndahl, L, Elvin, J, Castellot, J, Wei, L, Movérare-Skrtic, S, Ohlsson, C, Holm, L M, Bäckhed, G F, Syed, I, Bosch, F, Saghatelian, A, Kahn, B B, Hammarstedt, A & Smith, U 2017, ' Overexpressing the novel autocrine/endocrine adipokine WISP2 induces hyperplasia of the heart, white and brown adipose tissues and prevents insulin resistance ', Scientific Reports, vol. 7, 43515 . https://doi.org/10.1038/srep43515 |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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