| The Pro12Ala PPARgamma2 variant determines metabolism at the gene-environment interface. | |
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MedLine Citation:
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PMID: 19117549 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The metabolic impact of the common peroxisome proliferator-activated receptor gamma isoform 2 (PPARgamma2) variant Pro12Ala in human populations has been widely debated. We demonstrate, using a Pro12Ala knockin model, that on chow diet, Ala/Ala mice are leaner, have improved insulin sensitivity and plasma lipid profiles, and have longer lifespans. Gene-environment interactions played a key role as high-fat feeding eliminated the beneficial effects of the Pro12Ala variant on adiposity, plasma lipids, and insulin sensitivity. The underlying molecular mechanisms involve changes in cofactor interaction and adiponectin signaling. Altogether, our results establish the Pro12Ala variant of Ppargamma2 as an important modulator in metabolic control that strongly depends on the metabolic context. |
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Authors:
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Sami Heikkinen; Carmen Argmann; Jérôme N Feige; Hana Koutnikova; Marie-France Champy; Nassim Dali-Youcef; Eric E Schadt; Markku Laakso; Johan Auwerx |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell metabolism Volume: 9 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-01 Completed Date: 2009-02-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 88-98 Citation Subset: IM |
Affiliation:
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Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, 67404 Illkirch, France. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE13305 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adipose Tissue, White
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metabolism Alleles Amino Acid Substitution* Animals Body Mass Index Diet* Gene Expression Regulation Gene Knock-In Techniques Genetic Predisposition to Disease Glucose / metabolism* Insulin / metabolism Lipids / blood Longevity Mice Mutation PPAR gamma / genetics*, physiology* Protein Isoforms / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK067320-01/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Lipids; 0/PPAR gamma; 0/Protein Isoforms; 11061-68-0/Insulin; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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