| Ablation of Iqgap2 protects from diet-induced hepatic steatosis due to impaired fatty acid uptake. | |
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MedLine Citation:
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PMID: 21968151 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Long-chain fatty acids (LCFA) serve as structural components for membrane biogenesis and as primary energy sources during mitochondrial β-oxidation reactions. Hepatic LCFA uptake is complex, with characteristics suggestive of a dual-kinetic model manifested by rapid (carrier-assisted/facilitated) and delayed (passive diffusional) phases. Our previous work using mice deficient of the Iqgap2 gene established a highly novel link between IQGAP2, a putative GTPase-activating protein, and hepatocarcinogenesis. Now we report that Iqgap2 deficiency also results in selective loss of the facilitated phase of hepatocyte LCFA uptake with preservation of the diffusional component. This molecular defect was seen in Iqgap2(-/-) hepatocytes of all ages studied (1-, 4-, 8-months). The loss of facilitated LCFA uptake protected against development of hepatic triglyceride accumulation in Iqgap2-deficient mice fed high-fat diet, consistent with a fundamental role in physiological fat partitioning. These phenotypic changes could not be explained by genetic loss of fatty acid processing proteins known to regulate lipid uptake or metabolic processing pathways. Iqgap2-deficient livers also displayed enhanced insulin sensitivity. Conclusion: These observations identify a novel property of the putative GTPase-activating protein IQGAP2 in LCFA uptake in vitro and in vivo, and implicate IQGAP2 in an intracellular signaling pathway necessary for functional fatty acid uptake, lipid processing, and, possibly, glucose homeostasis. |
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Authors:
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Carmine S Chiariello; Joseph F Lacomb; Wadie F Bahou; Valentina A Schmidt |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-1 |
Journal Detail:
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Title: Regulatory peptides Volume: - ISSN: 1873-1686 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8100479 Medline TA: Regul Pept Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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