Project 467063

Cancer patients undergoing chemotherapy lose muscle mass. This often occurs concurrently with a pathological deposition of fat into the muscle, a condition known as myosteatosis. Muscle loss and myosteatosis each predict poorer outcomes and reduced survival in cancer patients. Cancer related myosteatosis is proposed to result from an imbalance in fatty acids uptake/utilization, which may involve mitochondria. Dr. Mazuraks research group revealed that eicosapentaenoic and docosahexaenoic acids (EPA+DHA) in fish oil attenuate muscle loss and myosteatosis in advanced cancer patients and a preclinical animal model of cancer.We aim to study the mechanisms driving cancer related myosteatosis. My research project consists of two parts: creation of a skeletal muscle cell culture model for myosteatosis, and exploring myosteatosis mechanisms with different cell environment conditions using this model. We will first purify stem cells from a human muscle biopsy to establish the primary cell model. After growing these stem cells into muscle cells, we will induce myosteatosis by adding plasma from colorectal cancer patients with or without chemotherapy to the cells. We will also add EPA+DHA to the cell media to confirm that myosteatosis is reduced. Validating this model enables further study of myosteatosis mechanisms using combinations of tumor cells, anti-neoplastic therapies and nutrients. Of these mechanisms, we will focus on: fatty acid uptake by muscle cells and mitochondria; mitochondrial capacity to use fatty acids to produce energy; and fatty acid synthesis.Revealing the mechanism by which EPA+DHA protects muscle cells from myosteatosis may provide insights leading to strategies to prevent myosteatosis in cancer patients, improving their survival and quality of life.