Khamoui 2020 Physiol Genomics

From Bioblast
Publications in the MiPMap
Khamoui AV, Tokmina-Roszyk D, Rossiter HB, Fields GB, Visavadiya NP (2020) Hepatic proteome analysis reveals altered mitochondrial metabolism and suppressed acyl-CoA synthetase-1 in colon-26 tumor-induced cachexia. Physiol Genomics 52:203-16.

Β» PMID: 32146873

Khamoui AV, Tokmina-Roszyk D, Rossiter HB, Fields GB, Visavadiya NP (2020) Physiol Genomics

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 non-muscle 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 pathways 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 to energetically inefficient inter-organ lactate cycling. Acyl-CoA synthetase-1 (ACSL1), known for activating long-chain fatty acids, was decreased in moderate and severe cachexia based on LC-MS/MS and immunoblotting. ACSL1 showed strong linear relationships with percent body weight change and muscle fiber size (R2=0.73-0.76, P<0.01). Mitochondrial coupling efficiency, which is compromised in cachexic livers to potentially increase energy expenditure and weight loss, also showed a linear relationship with ACSL1. These findings suggest altered mitochondrial and substrate metabolism of the liver in cancer cachexia, and possible hepatic targets for intervention. β€’ Keywords: STRING, TMT, Bioinformatics, Mitochondrial function, Quantitative proteomics β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: US FL Boca Raton Khamoui AV, US CA Torrance Rossiter HB

Labels: MiParea: Respiration  Pathology: Cancer 

Organism: Mouse  Tissue;cell: Liver  Preparation: Intact cells 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, NS  HRR: Oxygraph-2k 


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