CANCER CACHEXIA: METABOLIC CHANGES IN CARBOHYDRATE METABOLISM OF THE LIVER

Sarah M. Ramey*1, Megan E. Rosa-CaldwellƗ1, Jacob L. BrownƗ1, David E. LeeƗ1, Richard A. PerryƗ1, Wesley A. HaynieƗ1, Aaron R. CaldwellƗ1, Tyrone A. Washingtonǂ1, Michael P. Wiggsǂ2, Nicholas P. Greeneǂ1 1University of Arkansas, Fayetteville, Arkansas; 2Univeristy of Texas at Tyler, Tyler, Texas One negative side effect of cancer that dramatically affects cancer prognosis and progression is the development of cancer cachexia. Cancer cachexia is defined as cancer-associated muscle wasting. This is thought to be at least partially mediated by increased energy expenditure and is responsible for the death of 20-40% of all cancer patients. Although the liver is known to be the predominant regulator of whole body metabolism, there is little known about its relationship to the development of cancer cachexia. PURPOSE: The purpose of this exploratory study was to investigate alterations in liver metabolism by examining measures of glycogen storage throughout the progression of Lewis Lung Carcinoma (LLC) induced cancer cachexia. METHODS: C57BL/6J mice were injected with 1X106 LLC Cells in the left posterior leg, and the control group with phosphate buffered saline (PBS). The experimental groups included PBS, 1wk, 2wk, 3wk, and 4wk of cancer progression with 10-16 in each group. Sections of liver (n=~8/group) were cut and periodic acid-Schiff (PAS) stain for glycogen was completed. Images were analyzed for total area of stain as well as intensity of stain using NIS-Elements imaging software. A Welch’s one-way analysis of variance was used to determine differences between groups, a Tukey post hoc was used to determine differences between means. Significance was denoted at p\u3c0.05. RESULTS: 4wk animals had ~30% larger livers compared to all other groups with no other differences detected (~1000mg compared to ~1300mg, p\u3c0.05). However, there was no statistical differences detected between groups on either PAS area stained (~50% across groups, p\u3e0.05) or intensity of stain (Arbitrary Intensity Unit ~30 across groups, p\u3e0.05). Furthermore, neither glycogen area nor intensity correlated with liver size (r = 0.12 and r = 0.16 respectively). CONCLUSION: Differences in liver sizes are not attributable to glycogen storage. Though there were no differences in glycogen content, the increase in liver size suggests disruption of other processes in the liver. For future projects, we will further investigate mechanisms for liver hypertrophy in order to determine the relationship between the liver and cancer cachexia progression. This study was supported by The Arkansas Bioscience Institute and National Institutes of Health R15AR069913