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.

• MeSH
• Adipogenesis * MeSH
• Adiponectin metabolism   MeSH
• beta Catenin * metabolism   MeSH
• Cell Differentiation physiology   MeSH
• Glucose metabolism   MeSH
• Insulin metabolism   MeSH
• Bone Morphogenetic Proteins metabolism   MeSH
• Humans MeSH
• Mice MeSH
• Smad2 Protein MeSH
• Smad3 Protein MeSH
• Smad Proteins, Receptor-Regulated MeSH
• Growth Differentiation Factors metabolism   MeSH
• Wnt Signaling Pathway MeSH
• Receptor, Transforming Growth Factor-beta Type I MeSH
• Transforming Growth Factor beta metabolism   MeSH
• Adipocytes metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Adiponectin MeSH
• beta Catenin * MeSH
• GDF11 protein, human MeSH Browser
• Gdf11 protein, mouse MeSH Browser
• Glucose MeSH
• Insulin MeSH
• Bone Morphogenetic Proteins MeSH
• Smad2 Protein MeSH
• Smad3 Protein MeSH
• Smad Proteins, Receptor-Regulated MeSH
• Growth Differentiation Factors MeSH
• SMAD2 protein, human MeSH Browser
• Smad2 protein, mouse MeSH Browser
• SMAD3 protein, human MeSH Browser
• Smad3 protein, mouse MeSH Browser
• Receptor, Transforming Growth Factor-beta Type I MeSH
• TGFBR1 protein, human MeSH Browser
• Tgfbr1 protein, mouse MeSH Browser
• Transforming Growth Factor beta MeSH