| Hematopoietic AMPK β1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. | |
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MedLine Citation:
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PMID: 22080866 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Individuals who are obese are frequently insulin resistant, putting them at increased risk of developing type 2 diabetes and its associated adverse health conditions. The accumulation in adipose tissue of macrophages in an inflammatory state is a hallmark of obesity-induced insulin resistance. Here, we reveal a role for AMPK β1 in protecting macrophages from inflammation under high lipid exposure. Genetic deletion of the AMPK β1 subunit in mice (referred to herein as β1(-/-) mice) reduced macrophage AMPK activity, acetyl-CoA carboxylase phosphorylation, and mitochondrial content, resulting in reduced rates of fatty acid oxidation. β1(-/-) macrophages displayed increased levels of diacylglycerol and markers of inflammation, effects that were reproduced in WT macrophages by inhibiting fatty acid oxidation and, conversely, prevented by pharmacological activation of AMPK β1-containing complexes. The effect of AMPK β1 loss in macrophages was tested in vivo by transplantation of bone marrow from WT or β1(-/-) mice into WT recipients. When challenged with a high-fat diet, mice that received β1(-/-) bone marrow displayed enhanced adipose tissue macrophage inflammation and liver insulin resistance compared with animals that received WT bone marrow. Thus, activation of AMPK β1 and increasing fatty acid oxidation in macrophages may represent a new therapeutic approach for the treatment of insulin resistance. |
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Authors:
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Sandra Galic; Morgan D Fullerton; Jonathan D Schertzer; Sarah Sikkema; Katarina Marcinko; Carl R Walkley; David Izon; Jane Honeyman; Zhi-Ping Chen; Bryce J van Denderen; Bruce E Kemp; Gregory R Steinberg |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-11-14 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 121 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-02 Completed Date: 2012-01-31 Revised Date: 2012-02-07 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 4903-15 Citation Subset: AIM; IM |
Affiliation:
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St. Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Victoria, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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deficiency,
genetics,
physiology* Adipose Tissue / pathology* Animals Dietary Fats / toxicity Diglycerides / metabolism Enzyme Activation Fatty Acids / metabolism Hematopoietic Stem Cells / enzymology* Hepatitis / enzymology, pathology Insulin Resistance / physiology* Lymphocyte Activation Macrophages, Peritoneal / enzymology* Male Mice Mice, Knockout Mice, Obese Mitochondria / metabolism Obesity / enzymology* Oxidation-Reduction Phosphorylation Protein Processing, Post-Translational Radiation Chimera Specific Pathogen-Free Organisms T-Lymphocytes / pathology |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Dietary Fats; 0/Diglycerides; 0/Fatty Acids; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Prkab1 protein, mouse |
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