ESPEN 2022 Abstract Submission

Topic:      Nutrition and cancer

Abstract Submission Identifier: ESPEN22-ABS-2088

INSIGHTS INTO THE EFFECTS OF DIETARY EPA + DHA ON SKELETAL MUSCLE LIPID METABOLISM IN A PRECLINICAL MODEL OF COLORECTAL CANCER: A TRANSCRIPTOMICS APPROACH

P. Isesele^*, ¹, B. Bhatt ², S. Damaraju ², V. Mazurak ¹

¹Agricultural Food and Nutritional Sciences, ²Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada

Rationale: Myosteatosis is independently associated with poor outcomes and shortened survival in cancer patients, and this is exacerbated during chemotherapy treatment. Prior work has revealed that dietary EPA + DHA reverse chemotherapy-induced myosteatosis in an experimental model of colorectal cancer, but the mechanisms are not known. This study aimed to identify differentially regulated transcripts associated with lipid metabolism in the skeletal muscle in response to tumor, chemotherapy, and the effects of dietary EPA and DHA.

Methods: Female Fischer 344 rats bearing the Ward colon tumor were fed control diet and compared with experimental groups provided EPA +DHA (2.0 g /100 g of diet; the form of fish oil) initiated on the first day of chemotherapy. Rats received chemotherapy (irinotecan + 5-fluorouracil) 2 weeks after tumor implantation and were euthanized after 1 cycle (7d) and 2 cycles (14 d). Healthy rats without tumor served as a reference group (REF). Total RNA was extracted from gastrocnemius muscle and subjected to transcriptomic analysis using RNA-Seq. Differentially expressed genes were subjected to Ingenuity Pathway Analysis (IPA). Differential expression analysis was performed using DEseq2 (Fold-change cut-off ≥ 1.5 and P-value <0.05). Genes enriched in a pathway were identified and annotated for their putative functional role

Results: The top significant (p<0.05) canonical pathways identified in IPA analysis in the tumor bearing vs REF includes those relating to adipogenesius, white adipose tissue browing, and stearate biosynthesis. Furthermore, in the tumor + chemotherapy compared to REF, the top canonical pathways identified were Inflammation (Interleukin(IL)-3, 6, 8 12 signaling), 3-phosphoinositide degradation, and PPAR signalling. Upstream regulators activated by the tumor + chemotherapy were PPARG, LPL, IL-6, and IFNG. However, with the provision of EPA+DHA, the biological functions related to fat deposition (synthesis of lipids, transport of lipid and fatty acid metabolism) were decreased, and upstream regulators (TNF, PPARG, CEPB, IL-27) were inhibited. 

Conclusion: Provision of dietary EPA + DHA regulate pathways involved in lipid metabolism in the muscle. Collectively, these findings insight into the possibility of using EPA+DHA as concurrent therapy in cancer patients receiving chemotherapy to mitigate deleterious effects on muscle that are known to confer poor prognosis. 

Disclosure of Interest: None Declared

Keywords: cancer, lipids, myosteatosis, omega-3 fatty acid, transcriptomics