(P22-004-23) Effects of Dietary Linoleic Acid on Insulin Resistance and Loss of Adipose Tissue and Skeletal Muscle in a Mouse Model of Cancer Cachexia

Objectives: Cancer cachexia, characterized by depleted adipose tissue and muscle wasting, affects 30-80% of cancer patients. Prior studies indicate that insulin resistance contributes to the pathogenesis of cancer cachexia, and that linoleic acid (LA), an essential fatty acid, reduces insulin resistance in mice with cancer cachexia. This study will evaluate the effect of dietary LA on the development of cancer cachexia by measuring insulin resistance, adipose and muscle functional changes, mitochondrial function, and gene transcription changes in a mouse model.

Methods: In this 2x2 study design, 36 CD2F1 male mice will be randomized into 4 groups, fed a control or a LA fortified diet for 2 weeks, and followed by inoculating with 1x10^6 C26 adenocarcinoma cells or phosphate-buffered saline while continuing with respective diets. Body composition and insulin resistance will be measured during progression of the disease. Mice will be euthanized when mice exhibit 20% loss of the initial body weight, then muscle strength, mitochondrial function and gene expression in adipose and muscle tissues will be measured. A 2-way ANOVA will be used to analyze LA diet and tumor effects.

Results: Hypothesis: Tumor-bearing mice fed the LA-fortified diet will have lower insulin resistance compared to control diet fed mice, resulting in preserved adipose and muscle functions, efficient mitochondrial function, and longer time to reach weight loss criteria. Gene expression data will reveal novel information on how LA modulates metabolic pathways, contributing to effects during the pathogenesis of cachexia.

Conclusions: This study will provide valuable insights into the effects of dietary LA on energy metabolism and mitochondrial function during the progression of cancer cachexia.

Funding Sources: This project will be supported by the Ohio Agriculture Research and Development Center.