Restoring essential fatty acid balance improves muscle condition through mitochondria-associated mechanisms

Muscle loss (atrophy) and fatty infiltration of muscle (myosteatosis) are prevalent in people with cancer and are exacerbated during chemotherapy treatment. Each of these features are independently prognostic for survival in cancer patients. Ongoing work in the applicant’s laboratory has revealed an improvement in tumor response and reduced muscle loss when eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA) were provided to patients and in a pre-clinical model (rodents) undergoing cytotoxic treatment for cancer. The objective of this research is to develop an in vitro model to determine mechanisms by which EPA+DHA act on the mitochondria to protect muscle from development of atrophy and myosteatosis during exposure to chemotherapy. Human skeletal muscle cells are cultured with and without exposure to chemotherapeutic agents to establish the timeline and characteristics of myosteatosis. Cells cultured with or without EPA+DHA (at physiological levels) will be compared for triglyceride-fatty acid content, lipid droplet content and size, mitochondrial number, oxidative capacity and function. This information is required to develop or refine therapeutics directed at muscle wasting in cancer patients and contributes to collaborative efforts focused on improving prognosis of cancer patients.