To meet the constant energy requirement in the face of highly variable food supply, mammals employ intricate and precise mechanisms for energy storage. When total energy intake is in excess of energy expenditure such as after a meal, excess carbohydrates are converted to fatty acids (de novo lipogenesis). Excess fatty acids are then converted to triacylglycerol to be stored in adipose tissue and released as oxidative fuels for other tissues during times of energy need such as fasting and exercise.

The present invention describes for the first time that DNA-dependent protein kinase, DNA-PK, is connected to the signaling pathway involved in the formation of fat from carbohydrate in the liver. The enzymes that are involved in fatty acid and fat synthesis are tightly regulated during fasting/feeding. In the fed condition, especially after a high carbohydrate meal, activities of these enzymes drastically increase as blood glucose and insulin levels rise. The present invention demonstrates that DNA-PK regulates the transcription of fatty acid synthase (FAS), a central lipogenic enzyme that plays a crucial role in de novo lipogenesis by catalyzing all of the seven reactions involved in fatty acid synthesis. Therefore, DNA-PK is a pharmacological target for regulation of obesity and diabetes due to a diet high in carbohydrates.