The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth.
Cells
; 11(7)2022 03 24.
Article
in English
| MEDLINE | ID: covidwho-1785535
ABSTRACT
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Sarcopenia
/
End Stage Liver Disease
/
Non-alcoholic Fatty Liver Disease
Type of study:
Experimental Studies
Topics:
Long Covid
Limits:
Humans
Language:
English
Year:
2022
Document Type:
Article
Affiliation country:
Cells11071098
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