| Proatherogenic Abnormalities of Lipid Metabolism in SirT1 Transgenic Mice Are Mediated through Creb Deacetylation. | |
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MedLine Citation:
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PMID: 22078933 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Dyslipidemia and atherosclerosis are associated with reduced insulin sensitivity and diabetes, but the mechanism is unclear. Gain of function of the gene encoding deacetylase SirT1 improves insulin sensitivity and could be expected to protect against lipid abnormalities. Surprisingly, when transgenic mice overexpressing SirT1 (SirBACO) are placed on atherogenic diet, they maintain better glucose homeostasis, but develop worse lipid profiles and larger atherosclerotic lesions than controls. We show that transcription factor cAMP response element binding protein (Creb) is deacetylated in SirBACO mice. We identify Lys136 is a substrate for SirT1-dependent deacetylation that affects Creb activity by preventing its cAMP-dependent phosphorylation, leading to reduced expression of glucogenic genes and promoting hepatic lipid accumulation and secretion. Expression of constitutively acetylated Creb (K136Q) in SirBACO mice mimics Creb activation and abolishes the dyslipidemic and insulin-sensitizing effects of SirT1 gain of function. We propose that SirT1-dependent Creb deacetylation regulates the balance between glucose and lipid metabolism, integrating fasting signals. |
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Authors:
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Li Qiang; Hua V Lin; Ja Young Kim-Muller; Carrie L Welch; Wei Gu; Domenico Accili |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-9 |
Journal Detail:
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Title: Cell metabolism Volume: - ISSN: 1932-7420 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Naomi Berrie Diabetes Center, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA; Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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