Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c
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 ke...
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| Aineistotyyppi: | Artikkeli |
| Kieli: | en_US |
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Elsevier
2014
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| Linkit: | http://hdl.handle.net/1721.1/92248 https://orcid.org/0000-0002-1446-7256 |
| _version_ | 1826205291698454528 |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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 |
| author_sort | Wan, Min |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:10:23Z |
| format | Article |
| id | mit-1721.1/92248 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:10:23Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/922482022-10-01T13:30:07Z Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c 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 Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Koch Institute for Integrative Cancer Research at MIT Sabatini, David M. Guertin, David A. Peterson, Timothy R. 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. 2014-12-10T15:46:39Z 2014-12-10T15:46:39Z 2011-10 2011-06 Article http://purl.org/eprint/type/JournalArticle 15504131 http://hdl.handle.net/1721.1/92248 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. https://orcid.org/0000-0002-1446-7256 en_US http://dx.doi.org/10.1016/j.cmet.2011.09.001 Cell Metabolism Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | 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 Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c |
| title | Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c |
| title_full | Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c |
| title_fullStr | Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c |
| title_full_unstemmed | Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c |
| title_short | Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c |
| title_sort | postprandial hepatic lipid metabolism requires signaling through akt2 independent of the transcription factors foxa2 foxo1 and srebp1c |
| url | http://hdl.handle.net/1721.1/92248 https://orcid.org/0000-0002-1446-7256 |
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