[Frontiers in Bioscience E2, 87-97, January 1, 2010]

Trans-10,cis-12-CLA dysregulate lipid and glucose metabolism and induce hepatic NR4A receptors

Maria A. Navarro1,2,3, Lina Badimon1,3, Cristina Rodriguez1, Carmen Arnal3,4, Enda J. Noone5, Helen M. Roche5, Jesus Osada2,3, Jose Martinez-Gonzalez

1Centro de Investigacion Cardiovascular (CSIC-ICCC), Hospital de la Santa Creu i Sant Pau, c/Antoni MĒ Claret 167, 08025 Barcelona, Spain, 2Departamento de Bioquimica y Biologia Molecular y Celular, Facultad de Veterinaria, Instituto Aragones de Ciencias de la Salud (Universidad de Zaragoza-Direccion Salud del Gobierno de Aragon), Miguel Servet 177, 50013 Zaragoza, Spain, 3CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Spain, 4Departamento de Patologia Animal, Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain, 5Nutrigenomics Research Group, UCD Conway Institute, University College, Dublin, Ireland

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Material and methods
3.1. Animals and diets
3.2. Biochemical determinations and tissue isolation
3.3. Real-time PCR
3.4. Histological and immunohistochemical analysis
3.5. Statistical analysis
4. Results
4.1. Metabolic effects of CLA in ApoE-deficient mice
4.2. Effect of CLA on hepatic expression of NR4A receptors and genes involved in gluconeogenesis
4.3. Effect of CLA on hepatic content of fat and gene expression
5. Discussion
6. Acknowledgment
7. References

1. 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.