Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c
Author(s)Wan, Min; Leavens, Karla F.; Saleh, Danish; Easton, Rachael M.; Guertin, David A.; Peterson, Timothy R.; Kaestner, Klaus H.; Sabatini, David M.; Birnbaum, Morris J.; Sabatini, David; Peterson, Timothy Richard; ... Show more Show less
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Under conditions of obesity and insulin resistance, the serine/threonine protein kinase Akt/PKB is required for lipid accumulation in liver. Two forkhead transcription factors, FoxA2 and FoxO1, have been suggested to function downstream of and to be negatively regulated by Akt and are proposed as key determinants of hepatic triglyceride content. In this study, we utilize genetic loss of function experiments to show that constitutive activation of neither FoxA2 nor FoxO1 can account for the protection from steatosis afforded by deletion of Akt2 in liver. Rather, another downstream target positively regulated by Akt, the mTORC1 complex, is required in vivo for de novo lipogenesis and Srebp1c expression. Nonetheless, activation of mTORC1 and SREBP1c is not sufficient to drive postprandial lipogenesis in the absence of Akt2. These data show that insulin signaling through Akt2 promotes anabolic lipid metabolism independent of Foxa2 or FoxO1 and through pathways additional to the mTORC1-dependent activation of SREBP1c.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research; Koch Institute for Integrative Cancer Research at MIT
Wan, Min, Karla F. Leavens, Danish Saleh, Rachael M. Easton, David A. Guertin, Timothy R. Peterson, Klaus H. Kaestner, David M. Sabatini, and Morris J. Birnbaum. “Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c.” Cell Metabolism 14, no. 4 (October 2011): 516–527. © 2011 Elsevier Inc.
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