| Lecithin cholesterol acyltransferase null mice are protected from diet-induced obesity and insulin resistance in a gender-specific manner through multiple pathways. | |
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MedLine Citation:
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PMID: 21454561 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Complete lecithin cholesterol acyltransferase (LCAT) deficiency uniformly results in a profound HDL deficiency. We recently reported unexpected enhanced insulin sensitivity in LCAT knock-out mice in the LDL receptor knock-out background (Ldlr(-/-)×Lcat(-/-); double knock-out (DKO)), when compared with their Ldlr(-/-)×Lcat(+/+) (single knock-out (SKO)) controls. Here, we report that LCAT-deficient mice (DKO and Lcat(-/-)) are protected against high fat high sucrose (HFHS) diet-induced obesity without hypophagia in a gender-specific manner compared with their respective (SKO and WT) controls. The metabolic phenotypes are more pronounced in the females. Changes in endoplasmic reticulum stress were examined as a possible mechanism for the metabolic protection. The female DKO mice developed attenuated HFHS-induced endoplasmic reticulum stress as evidenced by a lack of increase in mRNA levels of the hepatic unfolded protein response (UPR) markers Grp78 and CHOP compared with SKO controls. The DKO female mice were also protected against diet-induced insulin resistance. In white adipose tissue of chow-fed DKO mice, we also observed a reduction in UPR, gene markers for adipogenesis, and markers for activation of Wnt signaling. In skeletal muscles of female DKO mice, we observed an unexpected increase in UCP1 in association with increase in phospho-AMPKα, PGC1α, and UCP3 expressions. This increase in UCP1 was associated with ectopic islands of brown adipocytes between skeletal muscle fibers. Our findings suggest that LCAT deficiency confers gender-specific protection against diet-induced obesity and insulin resistance at least in part through regulation in UPR, white adipose tissue adipogenesis, and brown adipocyte partitioning. |
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Authors:
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Lixin Li; Mohammad A Hossain; Sabreena Sadat; Lauren Hager; Lu Liu; Laetitia Tam; Stephanie Schroer; Lu Huogen; I George Fantus; Philip W Connelly; Minna Woo; Dominic S Ng |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-03-16 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-16 Completed Date: 2011-07-26 Revised Date: 2012-05-22 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 17809-20 Citation Subset: IM |
Copyright Information:
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© 2011 by The American Society for Biochemistry and Molecular Biology, Inc. |
Affiliation:
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Keenan Research Centre, Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, Toronto M5B 1W8, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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genetics,
metabolism Adipose Tissue, White / metabolism Animals Diet Dietary Fats / administration & dosage, adverse effects Female Heat-Shock Proteins / genetics, metabolism Insulin Resistance* Ion Channels / genetics, metabolism Lecithin Acyltransferase Deficiency / genetics, metabolism* Male Mice Mice, Knockout Mitochondrial Proteins / genetics, metabolism Muscle, Skeletal / metabolism Obesity / genetics, metabolism* Phosphatidylcholine-Sterol O-Acyltransferase / genetics, metabolism Receptors, LDL / genetics, metabolism* Sex Characteristics* Sucrose / administration & dosage, adverse effects Sweetening Agents / administration & dosage, adverse effects Trans-Activators / genetics, metabolism Transcription Factor CHOP / genetics, metabolism Unfolded Protein Response / genetics Wnt Proteins / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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MOP-191501//Canadian Institutes of Health Research; MOP-97979//Canadian Institutes of Health Research; MOP77527//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Ddit3 protein, mouse; 0/Dietary Fats; 0/Heat-Shock Proteins; 0/Ion Channels; 0/Mitochondrial Proteins; 0/Ppargc1a protein, mouse; 0/Receptors, LDL; 0/Sweetening Agents; 0/Trans-Activators; 0/Wnt Proteins; 0/mitochondrial uncoupling protein; 0/mitochondrial uncoupling protein 3; 0/molecular chaperone GRP78; 147336-12-7/Transcription Factor CHOP; 57-50-1/Sucrose; EC 2.3.1.43/Phosphatidylcholine-Sterol O-Acyltransferase; EC 2.7.11.1/AMP-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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