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Canadian Science Publishing, Applied Physiology, Nutrition, and Metabolism, 5(45), p. 500-512, 2020

DOI: 10.1139/apnm-2019-0407

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Hepatic alterations during the development and progression of cancer cachexia

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Cancer-associated bodyweight loss (cachexia) is a hallmark of many cancers and is associated with decreased quality of life and increased mortality. Hepatic function can dramatically influence whole-body energy expenditure and may therefore significantly influence whole-body health during cancer progression. The purpose of this study was to examine alterations in markers of hepatic metabolism and physiology during cachexia progression. Male C57BL/6J mice were injected with 1 × 106 Lewis Lung Carcinoma cells dissolved in 100 μL PBS and cancer was allowed to develop for 1, 2, 3, or 4 weeks. Control animals were injected with an equal volume of phosphate-buffered saline. Livers were analyzed for measures of metabolism, collagen deposition, protein turnover, and mitochondrial quality. Animals at 4 weeks had ∼30% larger livers compared with all other groups. Cancer progression was associated with altered regulators of fat metabolism. Additionally, longer duration of cancer development was associated with ∼3-fold increased regulators of collagen deposition as well as phenotypic collagen content, suggesting increased liver fibrosis. Mitochondrial quality control regulators appeared to be altered before any phenotypic alterations to collagen deposition. While induction of Akt was noted, downstream markers of protein synthesis were not altered. In conclusions, cancer cachexia progression is associated with hepatic pathologies, specifically liver fibrosis. Alterations to mitochondrial quality control mechanisms appear to precede this fibrotic phenotype, potentially suggesting mitochondrial mechanisms for the development of hepatic pathologies during the development and progression of cancer cachexia. Novelty Cachexia progression results in liver collagen deposition and fibrosis. Alterations in mitochondrial quality control may precede liver pathologies during cachexia.