Researchers identify genetic pathway involved in fat storage that may predispose individuals to type 2 diabetes

The discovery of a new genetic pathway that controls the storage of energy as fat and its subsequent expenditure could lead to the development of new medications aimed at treating metabolic conditions like obesity and type 2 diabetes, says a group of researchers from the Salk Institute for Biological Studies.

After analyzing the metabolic processes of fruit flies, the scientists reported in the journal Cell that the gene SIK3, which is shared by both flies and humans, silences a protein called FOXO after eating. This protein functions as a genetic switch and instructs the body to begin using its stores of fat for energy during periods of food scarcity or fasting.

The FOXO protein is active, for example, during overnight periods. While the body is deprived of food for six to eight hours, the protein instructs certain genes that are involved in metabolic processes to begin using fat stores for energy. The researchers speculated that if the FOXO protein were always switched on, individuals would burn much more fat.



To prove this theory, they engineered fruit flies to lack the SIK3 gene. These flies had significantly lower stores of bodily fat compared to genetically normal insects. A closer analysis of these flies showed that they had much higher expression of the FOXO protein.



The researchers speculated that humans who become obese and develop type 2 diabetes may have mutations in the genes involved in the process that results in excessive storage of fat. Solving this problem could lead to major gains in public health.

"Currently, we have over 20 million people with type 2 diabetes and close to 60 million with insulin resistance," said Marc Montminy, MD, PhD, and lead author of the study. "Finding a way to curb obesity will essentially require consideration of both environmental and genetic factors."
 
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