The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth.
The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth.
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DOI：
10.3390/cells11071098
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发表时间：
2022-03-24
期刊：
影响因子：
6
通讯作者：
Breen L
中科院分区：
文献类型：
--
作者：
Allen SL;Seabright AP;Quinlan JI;Dhaliwal A;Williams FR;Fine NHF;Hodson DJ;Armstrong MJ;Elsharkaway AM;Greig CA;Lai YC;Lord JM;Lavery GG;Breen L
肌肉减少症是影响肝病患者的常见并发症，但其潜在机制仍不清楚。我们的目的是阐明细胞机制，驱动肌肉减少症的进展，使用肝脏疾病的体外模型。将C2 C12肌管血清和氨基酸饥饿1小时，随后用来自四名非酒精性脂肪性肝病患者（NAFLD）、四名失代偿终末期肝病患者（ESLD）和四名年龄匹配的健康对照（CON）的禁食离体血清调节4小时或24小时。4小时后，用合成代谢刺激（5 mM亮氨酸）处理C2 C12肌管30分钟。与CON（−45%）和NAFLD（−35%;两者p < 0.001）相比，ESLD血清处理后肌管直径减小。与CON相比，在用NAFLD和ESLD血清调节的肌管中鉴定出最大线粒体呼吸（分别为24%和29%）、偶联效率（~12%）和线粒体自噬（~13%）的降低（两者均为p < 0.05）。与CON相比，ESLD血清治疗的肌管中肌生长抑制素（43%，p = 0.04）和MuRF-1（41%，p = 0.03）蛋白含量升高。在这里，我们强调了一种新的实验平台，以进一步探索与肝脏疾病相关的循环标志物的变化，这些标志物可能会导致肌肉减少症并开发靶向治疗干预措施。
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.
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DOI：
10.1002/jcsm.12232
发表时间：
2017-12
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Brown JL;Rosa-Caldwell ME;Lee DE;Blackwell TA;Brown LA;Perry RA;Haynie WS;Hardee JP;Carson JA;Wiggs MP;Washington TA;Greene NP
通讯作者：
Greene NP
影响因子：
3.7
作者：
Kim G;Kang SH;Kim MY;Baik SK
通讯作者：
Baik SK
影响因子：
5.5
作者：
Allen, Sophie L.;Marshall, Ryan N.;Breen, Leigh
通讯作者：
Breen, Leigh
影响因子：
24.5
作者：
Foucher, J;Chanteloup, E;de Lédinghen, V
通讯作者：
de Lédinghen, V
影响因子：
4.8
作者：
Kant, Sashi;Davuluri, Gangarao;Dasarathy, Srinivasan
通讯作者：
Dasarathy, Srinivasan