Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Vosko, L.
Impact of FGF21 on tissue signaling & metabolism
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2024. pp. 79
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Fickert Peter
- Moustafa Tarek
- Altmetrics:
- Abstract:
- Fibroblast growth factor 21 (FGF21) is a polypeptide hormone and member of the atypical FGF 15/19 subfamily. In contrast to other FGFs, members of the FGF 15/19 subfamily are endocrine peptides, able to travel through the blood stream. FGF21 is mostly produced and secreted by the liver and is known for its beneficial metabolic effects regarding weight loss and glycemic control. We developed a modified murine FGF21 (modFGF21) that should show a higher formulation stability for future scientific use in mouse models. Although FGF21 research has illuminated a variety of effects on metabolism in liver and adipose tissue, no study to date has examined these relations in cell culture and organ explants with our newly developed modFGF21. This diploma thesis was designed to test the performance of modFGF21 on cell culture and adipose organ explants from mice. Furthermore, this work assesses the hypothesis that organ explant culture can be utilized to demonstrate effects of FGF21 signaling. HUH7 cells were treated with different stocks of modFGF21 to test the performance on cell culture. In order to test the suitability of the adipose-tissue- organ explant culture, we extracted gonadal and inguinal white adipose tissue from C57BL/6 mice and treated with FGF21, isoproterenol or insulin. We tried out different treatment concentrations, media and treatment durations. To determine the impact of FGF21 signaling and lipolysis signaling we measured levels of key proteins using Western blot analysis and expression levels of key genes using RT-qPCR. Treatment of HUH7 cells with our modified murine FGF21 led to higher protein levels of phosphorylated extracellular-signal regulated kinases (pERK1/2). Stimulation of the explanted adipose tissue with isoproterenol and insulin led to elevated protein levels of phosphorylated hormone-sensitive lipase (pHSL) and phosphorylated protein kinase B (pAkt), respectively, both representing well-established downstream targets. However, there was no difference in pERK1/2 protein levels in explanted adipose tissue treated with modFGF21 or recombinant purified FGF21, compared to vehicle. We could demonstrate that organ explant culture based on adipose tissue can be utilized to test different signaling cascades in lipid metabolism. Nevertheless, FGF21 could not induce a clear induction of pERK1/2 in adipose explant cultures, therefore new investigations are needed to develop a system that can be applied to FGF21.