VAV3 and metabolic syndrome: On the other hand, the metabolic syndrome that develops in Vav3–/– mice is caused by two separate, SNS-dependent inputs on the liver: (a) An extrinsic effect elicited by peripheral tissues that promotes a post-receptor insulin state, de novo lipogenesis, and liver steatosis in Vav3–/– mice, regardless of the type of diet used [63]; and (b) an intrinsic effect on the liver itself that causes the upregulation of Pgc1α, a transcriptional cofactor involved in the activation of gluconeogenic, fatty acid oxidation, and ketogenic routes during fasting responses [63].