The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth
Sophie L. Allen,
Alex P. Seabright,
Jonathan I. Quinlan,
Amritpal Dhaliwal,
Felicity R. Williams,
Nicholas H. F. Fine,
David J. Hodson,
Matthew J. Armstrong,
Ahmed M. Elsharkaway,
Carolyn A. Greig,
Yu-Chiang Lai,
Janet M. Lord,
Gareth G. Lavery,
Leigh Breen
Affiliations
Sophie L. Allen
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK
Alex P. Seabright
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK
Jonathan I. Quinlan
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK
Amritpal Dhaliwal
National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK
Felicity R. Williams
National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK
Nicholas H. F. Fine
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, UK
David J. Hodson
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, UK
Matthew J. Armstrong
National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK
Ahmed M. Elsharkaway
National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK
Carolyn A. Greig
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK
Yu-Chiang Lai
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK
Janet M. Lord
National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK
Gareth G. Lavery
National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK
Leigh Breen
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK
Sarcopenia is a common complication affecting liver disease patients, yet the underlying mechanisms remain unclear. We aimed to elucidate the cellular mechanisms that drive sarcopenia progression using an in vitro model of liver disease. C2C12 myotubes were serum and amino acid starved for 1-h and subsequently conditioned with fasted ex vivo serum from four non-cirrhotic non-alcoholic fatty liver disease patients (NAFLD), four decompensated end-stage liver disease patients (ESLD) and four age-matched healthy controls (CON) for 4- or 24-h. After 4-h C2C12 myotubes were treated with an anabolic stimulus (5 mM leucine) for 30-min. Myotube diameter was reduced following treatment with serum from ESLD compared with CON (−45%) and NAFLD (−35%; p p p = 0.04) and MuRF-1 (41%, p = 0.03) protein content was elevated in myotubes treated with ESLD serum compared with CON. Here we highlight a novel, experimental platform to further probe changes in circulating markers associated with liver disease that may drive sarcopenia and develop targeted therapeutic interventions.
