Adiponectin: Potential therapeutic target for the treatment of muscle wasting in chronic heart failure - In vitro exploration
19 september 2016
UAntwerpen, Campus Drie Eiken, Building Q, Promotiezaal - Universiteitsplein 1 - 2610 Wilrijk (route: UAntwerpen, Campus Drie Eiken
Organisatie / co-organisatie:
Faculty of Medicine and Health Sciences
Prof C. Vrints & Prof V. Hoymans
PhD defence Tahnee Sente - Faculty of Medicine and Health Sciences
Skeletal muscle wasting and adiponectin resistance are two important features of HFrEF. In this thesis we introduced the use of primary cultures from the skeletal muscle of HFrEF patients as a tool to investigate the underlying mechanisms of adiponectin resistance and muscle wasting. We show that myoblasts from HFrEF patients have a diminished proliferative activity, which is strongly correlated with in vivo clinical parameters of functional capacity, yet myoblasts from HFrEF patients also exhibit a reduced anti-inflammatory activity. In addition, an impaired STAT3/TNFR2 signalling in the skeletal muscle of patients with HFrEF was indicated and associated with increased systemic inflammation. We demonstrate that exposure of primary cell cultures from healthy subjects to the pro-inflammatory cytokine TNF-α leads to deterioration of adiponectin signalling, myogenesis and mitochondrial biogenesis, impairments which are similar to those seen in patients with HFrEF. Silencing of AdipoR1 in healthy donor cultures attenuates myoblasts proliferation and AMPK activation. Overall, our findings indicate that adiponectin resistance and skeletal muscle dysfunction in HFrEF primarily emanate, albeit not necessary exclusively, from an increased inflammatory constitution. Further research is needed to fully elucidate and understand the interrelations between inflammation, adiponectin and muscle wasting in HFrEF. In the end, new insights may open up new avenues in the treatment of patients with HFrEF.