fatty acid oxidation and muscle atrophy in cancer

Cachexia is characterized by weight loss involving depletion of host adipose tissue and skeletal muscle mass. The word “cachexia” is derived from the Greek “kakos” meaning “bad” and “hexis” meaning “condition”. it is most commonly observed in individuals with advanced cancer, presenting in 80% of these patients, and it is one of the primary causes of morbidity and mortality associated with cancer.Additionally,although many people with cachexia show hypermetabolism, the causative role of metabolism in muscle atrophy has been unclear.

Although often associated with preterminal patients bearing disseminated disease, cachexia may be present in the early stages of tumor growth before any signs or symptoms of malignancy.  AThe central problem of cancer cachexia is that energy balance is not maintained, and the host has a relative hypophagia which results in host tissue wasting.  The tumor by its nature and obligate growth can continue to consume glucose, amino acids, and lipids at the expense of the host. This produces abnormal host intermediary metabolism including elevated glucose production and recycling, decreased muscle protein synthesis, and increased muscle and fat breakdown.These metabolic changes result in muscle wasting in adult cancer patients and growth failure in pediatric cancer patients. Host tissues are catabolized to meet the nutritional demands of tumor, and nutritional death may ensue. in this study, Tomoya Fukawa and et al shows that cachectic cancer cells secreted many inflammatory factors that increase fatty acid metabolism and activate p38 , before manifestation of cachectic muscle atrophy occurred.this factors induce excessive fatty acid oxidation which cause oxidative stress, p38 activation and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also improved muscle mass and body weight in cancer cachexia models in vivo. Therefore, fatty acid–induced oxidative stress could be targeted to prevent cancer-induced cachexia.

Saturday 18 February 2017