Role of FoxO proteins in the regulation of skeletal muscle anabolism, catabolism and insulin sensitivity

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Loss of muscle tissue or muscle wasting is a hallmark of many common health problems including diabetes, cancer, Cushing's syndrome, sepsis, HIV-Aids and renal failure. In the past 2-3 years important progress has been made in understanding the molecular regulation of both catabolism (muscle wasting) and anabolism (muscle growth) within mammalian skeletal muscles. It has been known for some time that a certain family of transcription factors, known as FoxO proteins, activate catabolic pathways. However, recently, we have shown that FoxO proteins also cause muscle wasting by blocking anabolic pathways. Our new data heighten the importance of targeting FoxO proteins are therapeutics for human diseases where muscle tissue wasting occurs. This proposal will investigate methods that will allow for blocking the action of FoxO proteins in the hope that muscle wasting can be prevented.