Alteration of lipid metabolism has been increasingly recognized as a hallmark of obesity andobesity-related diseases, i.e. cancer. Oncogenic growth signaling upregulates glycolysis, lipogenesis and glutamine metabolism to meet the biosynthetic demands of rapidly proliferating tumor cells.  However, how cancer cells manipulate glucose, lipid and glutamine metabolism is unclear. The metabolic sensor AMPK is stimulated upon fasting, exercise and calorie restriction to augment lipid and glucose metabolism. Oncogenic Myc has been shown to favor the conversion of glucose to lactate and increase the usage of glutamine in cancer cells. Given that metabolic reprogramming is modulated by circadian-, nutritional-, and environmental-driven molecular signals, epigenetic alterations of metabolic gene expression are dynamic and reversible. Recently, we have discovered that Myc functions as an epigenetic regulator to increase the expression of glutamine synthetase. Therefore, we are interested in investigating mechanotransduction (i.e., AMPK and Myc signaling), transcriptional and epigenetic regulation of lipogenesis and glutamine metabolismin in adipocytes, hepatocytes and cancer cells. Our long term goal is to determine the key enzymes for targeting in cancer metabolism and translation to the clinic.