Hepatic proteome analysis reveals altered mitochondrial metabolism and suppressed acyl-CoA synthetase-1 in colon-26 tumor-induced cachexia.

Physiological Genomics
Andy V KhamouiNishant P Visavadiya

Abstract

Cachexia is a life-threatening complication of cancer traditionally characterized by weight loss and muscle dysfunction. Cachexia, however, is a systemic disease that also involves remodeling of nonmuscle organs. The liver exerts major control over systemic metabolism, yet its role in cancer cachexia is not well understood. To advance the understanding of how the liver contributes to cancer cachexia, we used quantitative proteomics and bioinformatics to identify hepatic pathways and cellular processes dysregulated in mice with moderate and severe colon-26 tumor-induced cachexia; ~300 differentially expressed proteins identified during the induction of moderate cachexia were also differentially regulated in the transition to severe cachexia. KEGG pathway enrichment revealed representation by oxidative phosphorylation, indicating altered hepatic mitochondrial function as a common feature across cachexia severity. Glycogen catabolism was also observed in cachexic livers along with decreased pyruvate dehydrogenase protein X component (Pdhx), increased lactate dehydrogenase A chain (Ldha), and increased lactate transporter Mct1. Together this suggests altered lactate metabolism and transport in cachexic livers, which may contribute ...Continue Reading

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Citations

Aug 17, 2020·Molecular and Cellular Biochemistry·Nishant P VisavadiyaAndy V Khamoui
Nov 4, 2020·Pharmacological Reports : PR·Tamhida Masi, Bhoomika M Patel
Nov 19, 2020·International Journal of Molecular Sciences·Elisabeth WyartPaolo E Porporato
Feb 19, 2021·Journal of Cachexia, Sarcopenia and Muscle·Sarah A PötgensLaure B Bindels
Apr 4, 2021·International Journal of Molecular Sciences·Steffen H RaunLykke Sylow
Jun 16, 2021·Cell Biochemistry and Function·Nishant P VisavadiyaAndy V Khamoui
Sep 16, 2021·Journal of Cachexia, Sarcopenia and Muscle·Preeti Lakshman KumarUNKNOWN COPDGene, ECLIPSE and SPIROMICS investigators

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Methods Mentioned

BETA
light microscopy

Software Mentioned

Image Laboratory
Morpheus
STRING
Maxquant
ImageJ

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