Mice were placed on a low (4.5% fat) or a high-fat diet (HFD; 45% fat) for 12 weeks to induce fatty liver, after which the livers were sliced and cultured to collect secretion products (conditioned medium; CM). To investigate the effect of the secretome of a fatty liver on skeletal muscle metabolism, secretion products from a lean and fatty liver were placed on muscle cells for 24 h. Glucose uptake, protein synthesis, protein breakdown, and gene expression were subsequently measured. Glucose uptake in muscle cells was not different between chow and HFD CM in the basal state. However, insulin increased glucose uptake by 46% in muscle cells exposed to chow CM and by 18% in muscle cells exposed to HFD CM, demonstrating impaired insulin sensitivity in the muscle cells incubated with HFD CM . Protein synthesis was not different muscle cells incubated with chow and HFD CM, but protein breakdown was increased by 27% in HFD CM compared with chow CM. RNA profiling showed that 197 genes were differentially expressed, of which 46 (23.4%) were upregulated and 151 (76.6%) were downregulated by HFD CM compared with chow CM. Pathway analysis revealed that pathways related to skeletal muscle metabolism, growth, and remodeling were affected. This study provided evidence that secretion products from a fatty liver increase muscle protein breakdown rates and affects pathways involved in muscle function and morphology. The study supports our hypothesis that a fatty liver contributes to the development of muscle atrophy in individuals with NAFLD.
Science and teaching: Results that have been obtained during the funding period of the Marie Curie, have been published in high impact specialized peer-reviewed international journals and presented at national and international scientific symposium/ conferences. I have incorporated the results of my studies in my teaching program. Clinicians: In addition to a broad scientific outreach, I communicate my finding to specialists and other care providers who work with NAFLD patients in hospitals. Through my collaborator, Prof. Olde Damink, I have be able to present my work to a larger network of gastroenterologists and hepatologists at MUMC+ and in the region. I have also presented my data at the MUMC+ science days, thereby targeting researchers, clinicians, nurses and supporting staff. Patients: I am in good contact with Mrs. J. Willemse, who is the chair of the Dutch liver patient association, and whom I have met during a NAFLD conference in 2018. We have planned a meeting in December 2021 to discuss how to bring the results of my latest study across to the members of the association. General public: I ensure that the outcomes of my studies will reach the general public. I collaborated with the Press and Science communications department of Maastricht University and have issued a “press release” to have results disseminated in magazines, newspapers. This information reaches affected individuals, health departments, researchers, policy makers, and health advocacy groups.
