Article ; Online: GDF11 inhibits adipogenesis and improves mature adipocytes metabolic function via WNT/β-catenin and ALK5/SMAD2/3 pathways.
2022 Volume 55, Issue 10, Page(s) e13310
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Adipocytes/metabolism ; Adipogenesis ; Adiponectin/metabolism ; Animals ; Bone Morphogenetic Proteins/metabolism ; Cell Differentiation/physiology ; Glucose/metabolism ; Growth Differentiation Factors/metabolism ; Humans ; Insulin/metabolism ; Mice ; Receptor, Transforming Growth Factor-beta Type I ; Smad Proteins, Receptor-Regulated ; Smad2 Protein ; Smad3 Protein ; Transforming Growth Factor beta/metabolism ; Wnt Signaling Pathway ; beta Catenin/metabolism | |||||
| Chemical Substances | Adiponectin ; Bone Morphogenetic Proteins ; GDF11 protein, human ; Gdf11 protein, mouse ; Growth Differentiation Factors ; Insulin ; SMAD2 protein, human ; SMAD3 protein, human ; Smad Proteins, Receptor-Regulated ; Smad2 Protein ; Smad2 protein, mouse ; Smad3 Protein ; Smad3 protein, mouse ; Transforming Growth Factor beta ; beta Catenin ; Receptor, Transforming Growth Factor-beta Type I (EC 2.7.11.30) ; TGFBR1 protein, human (EC 2.7.11.30) ; Tgfbr1 protein, mouse (EC 2.7.11.30) ; Glucose (IY9XDZ35W2) | |||||
| Language | English | |||||
| Publishing date | 2022-08-03 | |||||
| Publishing country | England | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 1064202-x | |||||
| ISSN | 1365-2184 ; 0008-8730 ; 0960-7722 | |||||
| ISSN (online) | 1365-2184 | |||||
| ISSN | 0008-8730 ; 0960-7722 | |||||
| DOI | 10.1111/cpr.13310 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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