The Impact of Pancreatic Cancer Glutamine Transporter Downregulation on Cachexia and Visceral Organ Metabolism

Motivation: We previously identified alterations in brain and plasma glutamine/ glutamate with cachexia that led us to downregulate the glutamine transporter, SLC1A5, in the cachexia-inducing patient derived Pa04C PDAC cells. Goal(s): Targeting the glutamine transporter represents a promising approach to delay tumor progression and establish a novel treatment strategy in PDAC cachexia. Approach: We performed 1H MRS to determine the metabolic changes in multiple organs of mice. Results: We identified metabolic differences in organs of mice bearing SLC1A5 downregulated tumors compared to wild type or empty vector tumors. Our data identify SLC1A5 as a target to reduce PDAC induced cachexia and associated pathways Impact: By detecting these visceral organ metabolic changes we identified potential metabolic pathways that can be targeted to reduce cachexia.