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

Frohlich, Jan; Kovacovicova, Kristina; Raffaele, Marco; Virglova, Tereza; Cizkova, Eliska; Kučera,  Jan; Dobrovolná,  Julie; Wabitsch, Martin; Peyrou, Marion; Bonomini, Francesca; Rezzani, Rita; Chaldakov, George N.; Tonchev, Anton B.; Di Rosa, Michelino; Blavet,  Nicolas; Hejret,  Václav; Vinciguerra,  Manlio

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

Varování

Publikace nespadá pod Fakultu sportovních studií, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.

Autoři	FROHLICH Jan KOVACOVICOVA Kristina RAFFAELE Marco VIRGLOVA Tereza CIZKOVA Eliska KUČERA Jan DOBROVOLNÁ Julie WABITSCH Martin PEYROU Marion BONOMINI Francesca REZZANI Rita CHALDAKOV George N. TONCHEV Anton B. DI ROSA Michelino BLAVET Nicolas HEJRET Václav VINCIGUERRA Manlio
Rok publikování	2022
Druh	Článek v odborném periodiku
Časopis / Zdroj	Cell Proliferation
Fakulta / Pracoviště MU	Přírodovědecká fakulta
Citace
www	https://onlinelibrary.wiley.com/doi/10.1111/cpr.13310
Doi	http://dx.doi.org/10.1111/cpr.13310
Klíčová slova	DIFFERENTIATION FACTOR 11; ADIPOSE-TISSUE; SKELETAL-MUSCLE; TGF-BETA; CROSS-TALK; CELL; PROTEIN; WNT; AGE; ADIPONECTIN
Popis	GDF11 is a member of the TGF-beta 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. We performed microscopy imaging, biochemical and transcriptomic analyses of adipose tissues of 9 weeks old ob/ob mice and murine and human preadipocyte cell lines. 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/beta-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. 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.