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

Front Biosci (Elite Ed). 2010 Jan 1;2:87-97. doi: 10.2741/e69.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Linoleic Acids, Conjugated / 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

Substances

  • Blood Glucose
  • DNA-Binding Proteins
  • Linoleic Acids, Conjugated
  • Nerve Tissue Proteins
  • Nr4a1 protein, mouse
  • Nr4a2 protein, mouse
  • Nr4a3 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • trans-10,cis-12-conjugated linoleic acid
  • Glucose-6-Phosphatase
  • Phosphoenolpyruvate Carboxykinase (ATP)
  • Phosphopyruvate Hydratase
  • Pyruvate Carboxylase
  • Glucose