GDF11 inhibits adipogenesis and improves mature adipocytes metabolic function via WNT/β‐catenin and ALK5/SMAD2/3 pathways. Issue 10 (3rd August 2022)

• Record Type: Journal Article
• Authors: Frohlich, Jan; Kovacovicova, Kristina; Raffaele, Marco; Virglova, Tereza; Cizkova, Eliska; Kucera, Jan; Bienertova‐Vasku, Julie; Wabitsch, Martin; Peyrou, Marion; Bonomini, Francesca; Rezzani, Rita; Chaldakov, George N.; Tonchev, Anton B.; Di Rosa, Michelino; Blavet, Nicolas; Hejret, Vaclav; Vinciguerra, Manlio
• Is Part Of: Cell proliferation. Volume 55:Issue 10(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-03
• Subjects: Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.13310
• Languages: English
• ISSNs: 0960-7722

Abstract

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. Abstract : GDF11 activates distinct signaling pathways in pre‐adipocytes (β‐catenin) and in mature adipocytes (WNT pathway), to regulate adipogenesis and adiponectin secretion/insulin sensitivity, respectively.