The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth

Cells

David J. Hodson¹  Nicholas H. F. Fine¹  Janet M. Lord²  Felicity R. Williams²  Amritpal Dhaliwal²  Matthew J. Armstrong²  Ahmed M. Elsharkaway²  Gareth G. Lavery²  Sophie L. Allen³  Jonathan I. Quinlan³  Yu-Chiang Lai³  Leigh Breen³  Carolyn A. Greig³  Alex P. Seabright³ 

[1] Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, UK;National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK;School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK;

关键词: chronic liver disease;    sarcopenia;    leucine;    mitochondria;    protein breakdown;   

DOI  :  10.3390/cells11071098

来源: DOAJ

【 摘 要 】

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 < 0.001 for both). A reduction in maximal mitochondrial respiration (24% and 29%, respectively), coupling efficiency (~12%) and mitophagy (~13%) was identified in myotubes conditioned with NAFLD and ESLD serum compared with CON (p < 0.05 for both). Myostatin (43%, 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.

【 授权许可】

Unknown