GDF11 inhibits adipogenesis and improves mature adipocytes metabolic function via WNT/β-catenin and ALK5/SMAD2/3 pathways.

Autor: Frohlich J; International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic., Kovacovicova K; International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.; Psychogenics Inc, Tarrytown, New York, USA., Raffaele M; International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic., Virglova T; International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic., Cizkova E; International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic., Kucera J; Research Center for Toxic Compounds in the Environment (RECETOX), Masaryk University, Brno, Czech Republic., Bienertova-Vasku J; Research Center for Toxic Compounds in the Environment (RECETOX), Masaryk University, Brno, Czech Republic.; Faculty of Medicine, Department of Pathological Physiology, Masaryk University, Brno, Czech Republic., Wabitsch M; Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany., Peyrou M; Departament de Bioquímica i Biomedicina Molecular and Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain.; Centro de Investigación Biomédica en Red 'Fisiopatología de la Obesidad y Nutrición', Madrid, Spain.; Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain., Bonomini F; Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.; Interdepartmental University Center of Research 'Adaption and Regeneration of Tissues and Organs-(ARTO)', University of Brescia, Brescia, Italy., Rezzani R; Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.; Interdepartmental University Center of Research 'Adaption and Regeneration of Tissues and Organs-(ARTO)', University of Brescia, Brescia, Italy., Chaldakov GN; Department of Translational Stem Cell Biology, Research Institute of the Medical University, Varna, Bulgaria.; Department of Anatomy and Cell Biology, Research Institute of the Medical University, Varna, Bulgaria., Tonchev AB; Department of Translational Stem Cell Biology, Research Institute of the Medical University, Varna, Bulgaria.; Department of Anatomy and Cell Biology, Research Institute of the Medical University, Varna, Bulgaria., Di Rosa M; Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy., Blavet N; CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic., Hejret V; CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic.; National Center for Biomolecular Research, Masaryk University, Brno, Czech Republic., Vinciguerra M; International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.; Department of Translational Stem Cell Biology, Research Institute of the Medical University, Varna, Bulgaria.
Jazyk: angličtina
Zdroj: Cell proliferation [Cell Prolif] 2022 Oct; Vol. 55 (10), pp. e13310. Date of Electronic Publication: 2022 Aug 03.
DOI: 10.1111/cpr.13310
Abstrakt: Objective: GDF11 is a member of the TGF-β superfamily that was recently implicated as potential "rejuvenating" factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 signaling in the glucose homeostasis and in the differentiation of white adipose tissue.
Methods: We performed microscopy imaging, biochemical and transcriptomic analyses of adipose tissues of 9 weeks old ob/ob mice and murine and human pre-adipocyte cell lines.
Results: Our in vivo experiments employing GDF11 treatment in ob/ob mice showed improved glucose/insulin homeostasis, decreased weight gain and white adipocyte size. Furthermore, GDF11 treatment inhibited adipogenesis in pre-adipocytes by ALK5-SMAD2/3 activation in cooperation with the WNT/β-catenin pathway, whose inhibition resulted in adipogenic differentiation. Lastly, we observed significantly elevated levels of the adipokine hormone adiponectin and increased glucose uptake by mature adipocytes upon GDF11 exposure.
Conclusion: We show evidence that link GDF11 to adipogenic differentiation, glucose, and insulin homeostasis, which are pointing towards potential beneficial effects of GDF11-based "anti-obesity" therapy.
(© 2022 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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