Open Access
Article
Trans-10,cis-12-CLA dysregulate lipid and glucose metabolism and induce hepatic NR4A receptors
Maria A Navarro1,Lina Badimon1,Cristina Rodriguez1,Carmen Arnal1,Enda J Noone1,Helen M Roche1,Jesus Osada1,Jose Martinez-Gonzalez1
1
Centro de Investigacion Cardiovascular, Hospital de la Santa Creu i Sant Pau, c/Antoni Ma Claret 167, 08025 Barcelona, Spain
DOI: 10.2741/E69 Volume 2 Issue 1, pp.87-97
Published: 01 January 2010
Abstract

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.

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Maria A Navarro, Lina Badimon, Cristina Rodriguez, Carmen Arnal, Enda J Noone, Helen M Roche, Jesus Osada, Jose Martinez-Gonzalez. Trans-10,cis-12-CLA dysregulate lipid and glucose metabolism and induce hepatic NR4A receptors. Frontiers in Bioscience-Elite. 2010. 2(1); 87-97.