Cancer is an important health problem, which still remains raising the number of deaths related to this disease. Cachexia is responsible for 25-30% of all cancer-related deaths. Cancer-cachexia leads to involuntary weight loss, impaired quality of life, and poor prognosis. Nutritional leucine supplementation has been shown to preserve muscle mass in cancer cachectic patients, due to the capacity to increase protein synthesis in skeletal muscle. However, leucine can also stimuli proliferation and motility, potentially enhancing metastasis processess. Cancer cells have a unique metabolism as the abnormal mitochondrial function, which causes mainly glucose and glutamine fermentation by neoplastic cell to produce energy (Warburg effect) and also prevents ketone body utilization as energy source. So, dietary strategies that decrease blood glucose may reduce tumor cell growth and metastasis, reducing the glucose avaible and suppressing insulin signaling. One of these strategies is the Ketogenic diet, which is a high fat (75-85%), moderate protein (10-20%), low carbohydrate (5-10%) diet that reduces glucose (and insulin) and elevates the ketone bodies. The result is depletion of carbohydrate store as glycogen, reducing glucose availability, which suppresses the insulin signaling and elevates blood ketones, all processes associated with lower tumor growth. Although leucine can promote skeletal muscle growth, the effects of leucine in cancer growth and metastasis are still unclear. Therefore, this project aims to evaluate the effects of nutritional ketogenic+leucine supplementation on tumor growth and the cachexia state.
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