Tamping down expression of the fruit fly gene Indy improves mitochondrial function, mimicking the effects of a low-calorie diet and prolonging the life span of the flies (hence the name, an abbreviation for “I’m not dead yet”). But scientists have lacked details on the precise physiological bases for these changes.
To find out, a group led by Gerald I. Shulman, M.D., Ph.D., George R. Cowgill Professor of Physiological Chemistry and professor of Medicine and Cellular and Molecular Physiology, knocked out mINDY, a mammalian version of the gene. As reported In the August 3 issue of Cell Metabolism, the manipulation improved mitochondrial function and fatty acid metabolism in the liver. The mice were protected from diet- and age-related accumulation of fat in the liver, which leads to hepatic insulin resistance, and, in humans, can evolve into type 2 diabetes.
“mINDY may be a novel therapeutic target for the treatment of hepatic insulin resistance, a major factor in the pathogenesis of type 2 diabetes,” says Shulman, also a Howard Hughes Medical Institute investigator.