caspase were decreased after treatment with ANE f h

insulin activates the sterol regulatory element binding BAY 11-7082 protein transcription factor to promote hepatic lipogenesis. We find that this induction depends on the mammalian target of rapamycin complex 1. We generated mice with liver specific deletion of TSC1, which in insulin independent activation of mTORC1, to help define the role of mTORC1 in the regulation of SREBP1c in the liver. Remarkably, the LTsc1KO mice are guarded from diet and age induced hepatic steatosis and screen hepatocyte intrinsic defects in de novo lipogenesis and SREBP1c activation. These phenotypes result from attenuation of Akt signaling driven by mTORC1 dependent insulin resistance. For that reason, mTORC1 activation is not adequate to promote hepatic SREBP1c within the lack of Akt signaling, revealing the existence of one more downstream route also required for this induction. We offer evidence that mTORC1 independent pathway requires Akt mediated suppression of Insig2a, a liver specific transcript encoding the SREBP1c inhibitor INSIG2. The liver is Meristem a vital body within the systemic response to insulin, handling both glucose and lipid k-calorie burning. Hepatocytes respond to insulin by halting gluconeogenesis and growing de novo lipid synthesis. Genetic mouse models have demonstrated that both of these responses to insulin occur, at least partly, downstream of the protein kinase Akt2. Akt2 mediates these effects mainly through the regulation of two downstream transcription facets, FOXO1 and SREBP1c, which get a handle on the appearance of the metabolic enzymes underlying these processes. FOXO1 stimulates gluconeogenic gene expression in the liver and is immediately phosphorylated and inhibited by Akt. Whilst the components are less-well known, Akt signaling appears to stimulate de novo lipid synthesis through the activation of SREBP isoforms. SREBP1c could be the dominant insulin Adriamycin stimulated isoform in the liver responsible for promoting fatty acid synthesis and inducing lipogenic gene expression. Akt activation appears to be both necessary and adequate for the induction of hepatic SREBP1c and lipid accumulation. An essential characteristic of hepatic insulin signaling is that control of gluconeogenesis and lipogenesis is differentially afflicted under pathological conditions of insulin resistance associated with type 2 diabetes. Under such circumstances, insulin does not reduce glucose production by the liver, while the induction of hepatic lipogenesis is sustained, thereby adding to the hyperglycemic and hyperlipidemic states. Understanding this phenomenon, known as selective insulin resistance, needs a deeper understanding of how insulin and Akt regulate hepatic lipid kcalorie burning.