Document Detail


Trans-10,cis-12-CLA dysregulate lipid and glucose metabolism and induce hepatic NR4A receptors.
MedLine Citation:
PMID:  20036857     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Our aim was to assess the effect of two isomers of conjugated linoleic acids (CLA), cis-9,trans-11-CLA (c9,t11-CLA) and trans-10,cis-12-CLA (t10,c12-CLA), on glucose metabolism and hepatic expression of NR4A receptors, key transcription factors regulating gluconeogenesis. ApoE-deficient mice were fed isocaloric, isonitrogenous westernized diets enriched with c9,t11-CLA, t10,c12-CLA or linoleic acid (control diet). Plasma glucose, NEFA, triglyceride and cholesterol concentrations were significantly higher in the t10,c12-CLA group compared with c9,t11-CLA or control group. Plasma insulin concentrations were lowered by c9,t11-CLA compared with either control or t10,c12-CLA group. Hepatic expression of NR4A receptors (Nur77, Nurr1 and NOR-1) was induced by t10,c12-CLA while c9,t11-CLA had not effect. Consistently t10,c12-CLA up-regulated key genes involved in gluconeogenesis including glucose-6-phosphatase, enolase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase. Hepatic expression of NR4A receptors correlated with plasma NEFA, with the expression of their target gene fatty acid transporter (FAT)/CD36 and with the accumulation of fat in the liver. These results suggest that t10,c12-CLA promote dysregulation of lipid and glucose metabolism, at least in part, by an isomer-specific modulation of hepatic expression of NR4A receptors.
Authors:
Maria A Navarro; Lina Badimon; Cristina Rodriguez; Carmen Arnal; Enda J Noone; Helen M Roche; Jesus Osada; Jose Martinez-Gonzalez
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-01
Journal Detail:
Title:  Frontiers in bioscience (Elite edition)     Volume:  2     ISSN:  1945-0508     ISO Abbreviation:  Front Biosci (Elite Ed)     Publication Date:  2010  
Date Detail:
Created Date:  2009-12-28     Completed Date:  2010-07-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101485240     Medline TA:  Front Biosci (Elite Ed)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  87-97     Citation Subset:  IM    
Affiliation:
Centro de Investigacion Cardiovascular, Hospital de la Santa Creu i Sant Pau, c/Antoni Ma Claret 167, 08025 Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Blood Glucose
DNA-Binding Proteins / metabolism*
Gene Expression Regulation / drug effects*
Glucose / metabolism*
Glucose-6-Phosphatase / metabolism
Immunohistochemistry
Isomerism
Linoleic Acids, Conjugated / metabolism,  pharmacology*
Lipid Metabolism / drug effects*
Liver / metabolism
Mice
Mice, Mutant Strains
Nerve Tissue Proteins / metabolism*
Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
Nuclear Receptor Subfamily 4, Group A, Member 2 / metabolism*
Phosphoenolpyruvate Carboxykinase (ATP) / metabolism
Phosphopyruvate Hydratase / metabolism
Pyruvate Carboxylase / metabolism
Receptors, Steroid / metabolism*
Receptors, Thyroid Hormone / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/DNA-Binding Proteins; 0/Linoleic Acids, Conjugated; 0/Nerve Tissue Proteins; 0/Nr4a1 protein, mouse; 0/Nr4a2 protein, mouse; 0/Nr4a3 protein, mouse; 0/Nuclear Receptor Subfamily 4, Group A, Member 1; 0/Nuclear Receptor Subfamily 4, Group A, Member 2; 0/Receptors, Steroid; 0/Receptors, Thyroid Hormone; 0/trans-10,cis-12-conjugated linoleic acid; 50-99-7/Glucose; EC 3.1.3.9/Glucose-6-Phosphatase; EC 4.1.1.49/Phosphoenolpyruvate Carboxykinase (ATP); EC 4.2.1.11/Phosphopyruvate Hydratase; EC 6.4.1.1/Pyruvate Carboxylase

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