| PPAR-gamma response element activity in intact primary human adipocytes: effects of fatty acids. | |
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MedLine Citation:
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PMID: 16226011 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: We studied the activity and regulation of the peroxisome proliferator-activated receptor-gamma response element (PPRE) in primary human adipocytes. METHODS: We transfected primary human adipocytes with a plasmid-encoding firefly luciferase cDNA under control of a PPRE from the acyl-coenzyme A oxidase gene by using our newly developed electroporation-based method. Several fatty acids were added to the fat cells to study potential activation of peroxisome proliferator-activated receptor-gamma. RESULTS: Cells responded maximally to 5 microM of rosiglitazone at a 5.1 +/- 1.4-fold over basal increase in luciferase activity. There was a positive correlation between body mass index and the response to 5 microM of rosiglitazone (r = 0.36, P = 0.03). Patients with type 2 diabetes had similar basal PPRE activity but responded more strongly to 5 microM of rosiglitazone than did non-diabetic subjects (10.2 +/- 5-fold and 5.4 +/- 1-fold over basal increase, respectively, P < 0.0001). Among saturated fatty acids, lauric acid was without effect, but 10 microM of palmitic or stearic acid increased PPRE activity 20% to 35% above basal levels. Monounsaturated palmitoleic acid at 1 microM induced a PPRE transcriptional activity that corresponded to half the therapeutic levels of rosiglitazone. CONCLUSION: Adipocytes from obese subjects and patients with type 2 diabetes responded particularly strongly to the effect of rosiglitazone on PPRE. Because fatty acids in the diet can affect the transcriptional activity of peroxisome proliferator-activated receptor-gamma over decades, the stimulation induced by stearic and palmitoleic acids can affect insulin sensitivity and, hence, cardiovascular morbidity and mortality in humans. |
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Authors:
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Lilian Sauma; Karin G Stenkula; Preben Kjølhede; Peter Strålfors; Mats Söderström; Fredrik H Nystrom |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-10-12 |
Journal Detail:
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Title: Nutrition (Burbank, Los Angeles County, Calif.) Volume: 22 ISSN: 0899-9007 ISO Abbreviation: Nutrition Publication Date: 2006 Jan |
Date Detail:
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Created Date: 2006-02-03 Completed Date: 2006-07-31 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8802712 Medline TA: Nutrition Country: United States |
Other Details:
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Languages: eng Pagination: 60-8 Citation Subset: IM |
Affiliation:
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Diabetes Research Centre, Faculty of Health Sciences, Linköping University, Linköping, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipocytes
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metabolism* Cells, Cultured Diabetes Mellitus, Type 2 / metabolism Fatty Acid Transport Proteins Fatty Acids / pharmacology* Female Gene Expression Regulation Humans Hypoglycemic Agents / pharmacology Luciferases / genetics, metabolism* Middle Aged Obesity / metabolism PPAR gamma / drug effects*, metabolism* Thiazolidinediones / pharmacology* Transfection |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acid Transport Proteins; 0/Fatty Acids; 0/Hypoglycemic Agents; 0/PPAR gamma; 0/Thiazolidinediones; 122320-73-4/rosiglitazone; EC 1.13.12.-/Luciferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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