Massachusetts General Hospital (MGH) investigators have found that an enzyme with several important roles in energy metabolism also helps to turn off the body's generation of fats and cholesterol under conditions of fasting. The report in Genes & Development describes how SIRT1, one of a group of enzymes called sirtuins, suppresses the activity of a family of proteins called SREBPs, which control the body's synthesis and handling of fats and cholesterol. The findings could lead to new approaches to treating conditions involving elevated cholesterol and lipid levels.



"SIRT1 had previously been shown to act as an energy sensor, promoting the use of stored fat in response to food deprivation; however, its function in shutting down fat and cholesterol synthesis was unknown," says Amy Walker, PhD, of the MGH Cancer Center, the study's lead author. "These findings point to SIRT1 as a master regulator of physiologic energy stability that controls the synthesis and storage of fat, as well as its usage as fuel."



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