| PPARGC1A coding variation may initiate impaired NEFA clearance during glucose challenge. | |
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MedLine Citation:
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PMID: 17216277 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS/HYPOTHESIS: The peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein, encoded by the PPARGC1A gene, transcriptionally activates a complex pathway of lipid and glucose metabolism and is expressed primarily in tissues of high metabolic activity such as liver, heart and exercising oxidative skeletal muscle fibre. Ppargc1a-null mice develop systemic dyslipidaemia and hepatic steatosis. In humans, NEFAs downregulate PPARGC1A expression in skeletal muscle. Furthermore, a common non-synonymous coding variant at PPARGC1A (Gly482Ser, rs8192678) is associated with decreased PPARGC1A mRNA levels and increased type 2 diabetes risk. MATERIALS AND METHODS: In a population-based sample of 691 healthy middle-aged Europids we assessed whether Gly482Ser is associated with levels of NEFA when fasting and in response to an oral glucose challenge. We also assessed the potential effect-modifying role of adipose tissue mass on these phenotypes. RESULTS: After adjustment for age, sex, fat mass and fat-free mass, the Ser482 allele associated with higher NEFA at 30 min and 2 h and with NEFA AUC (all values p<or=0.02). Furthermore, suggestive evidence of interaction between fat mass and Gly482Ser was observed for fasting NEFA (p=0.059). After stratification by level of obesity, genotype associations were observed in the obese for fasting NEFA (p=0.028) and NEFA at 30 min (p=0.013) and 2 h (p=0.002), and with NEFA AUC (p=0.005), but no significant associations were observed in lean individuals (all values p>0.6). CONCLUSIONS/INTERPRETATION: Our observations indicate that NEFA clearance is blunted following a glucose load in carriers of the PPARCG1A Ser482 allele. This association is augmented by obesity. |
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Authors:
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P W Franks; U Ekelund; S Brage; J Luan; A J Schafer; S O'Rahilly; I Barroso; N J Wareham |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-01-10 |
Journal Detail:
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Title: Diabetologia Volume: 50 ISSN: 0012-186X ISO Abbreviation: Diabetologia Publication Date: 2007 Mar |
Date Detail:
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Created Date: 2007-02-06 Completed Date: 2007-09-26 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: Germany |
Other Details:
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Languages: eng Pagination: 569-73 Citation Subset: IM |
Affiliation:
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Genetic Epidemiology and Clinical Research Group, Department of Public Health and Clinical Medicine, Section for Medicine, Umeå University Hospital, Umeå, Sweden. paul.franks@medicin.umu.se |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipose Tissue
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anatomy & histology Adult Amino Acid Substitution Fatty Acids, Nonesterified / blood* Female Gene Frequency Genetic Variation* Genotype Heat-Shock Proteins / genetics* Humans Male Middle Aged Transcription Factors / genetics* Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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077016//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Nonesterified; 0/Heat-Shock Proteins; 0/PPARGC1A protein, human; 0/Transcription Factors |
| Comments/Corrections | |
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