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

Frohlich, Jan, Kovacovicova, Kristina, Raffaele, Marco, Virglova, Tereza, Cizkova, Eliska, Kucera, Jan, Bienertova-Vasku, Julie, Wabitsch, Martin, Peyrou, Marion, Bonomini, Francesca
et al (show 7 more authors) (2022) GDF11 inhibits adipogenesis and improves mature adipocytes metabolic function via WNT/β-catenin and ALK5/SMAD2/3 pathways. CELL PROLIFERATION, 55 (10). e13310-.

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<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.

Item Type: Article
Uncontrolled Keywords: Adipocytes, Animals, Humans, Mice, Insulin, Glucose, Transforming Growth Factor beta, Bone Morphogenetic Proteins, Cell Differentiation, Adipogenesis, beta Catenin, Smad Proteins, Receptor-Regulated, Smad2 Protein, Smad3 Protein, Adiponectin, Growth Differentiation Factors, Wnt Signaling Pathway, Receptor, Transforming Growth Factor-beta Type I
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 20 Jan 2023 09:41
Last Modified: 05 Oct 2023 18:02
DOI: 10.1111/cpr.13310
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