Isomer-dependent metabolic effects of conjugated linoleic acid: insights from molecular markers sterol regulatory element-binding protein-1c and LXRalpha.

Abstract

Conjugated linoleic acid (CLA) is a heterogeneous group of positional and geometric isomers of linoleic acid. This study demonstrates the divergent effects of the cis-9 trans-11 (c9,t11-CLA) and trans-10 cis-12 (t10,c12-CLA) isomers of CLA on lipid metabolism and nutrient regulation of gene expression in ob/ob mice. The c9, t11-CLA diet decreased serum triacylglycerol (P = 0.01) and nonesterified fatty acid (NEFA) (P = 0.05) concentrations, and this was associated with reduced hepatic sterol regulatory element-binding protein-1c (SREBP-1c; P = 0.0045) mRNA expression, coupled with reduced levels of both the membrane-bound precursor and the nuclear forms of the SREBP-1 protein. C9,t11-CLA significantly reduced hepatic LXRalpha (P = 0.019) mRNA expression, a novel regulator of SREBP-1c. In contrast, c9,t11-CLA increased adipose tissue SREBP-1c mRNA expression (P = 0.0162) proportionally to the degree of reduction of tumor necrosis factor alpha (TNF-alpha) mRNA (P = 0.012). Recombinant TNF-alpha almost completely abolished adipose tissue SREBP-1c mRNA expression in vivo. The t10,c12-CLA diet promoted insulin resistance and increased serum glucose (P = 0.025) and insulin (P = 0.01) concentrations. T10, c12-CLA induced profound weight loss (P = 0.0001) and increased brown and white adipose tissue UCP-2 (P = 0.001) and skeletal muscle UCP-3 (P = 0.008) mRNA expression. This study highlights the contrasting molecular and metabolic effect of two isomers of the same fatty acids. The ameliorative effect of c9,t11-CLA on lipid metabolism may be ascribed to reduced synthesis and cleavage of hepatic SREBP-1, which in turn may be regulated by hepatic LXRalpha expression.

• Authors: Helen M Roche, Enda Noone, Ciaran Sewter, Siobhan Mc Bennett, David Savage, Michael J Gibney, Stephen O'Rahilly, Antonio J Vidal-Puig
• Journal: Diabetes (Diabetes) Vol. 51 Issue 7 Pg. 2037-44 (Jul 2002) ISSN: 0012-1797 [Print] United States
• PMID: 12086931 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• CCAAT-Enhancer-Binding Proteins
• DNA-Binding Proteins
• Insulin
• Linoleic Acids
• Lipids
• Liver X Receptors
• Nr1h3 protein, mouse
• Orphan Nuclear Receptors
• Receptors, Cytoplasmic and Nuclear
• Srebf1 protein, mouse
• Sterol Regulatory Element Binding Protein 1
• Transcription Factors
• Triglycerides

Topics

• Animals
• Blood Glucose (drug effects, metabolism)
• CCAAT-Enhancer-Binding Proteins (metabolism)
• DNA-Binding Proteins (metabolism)
• Diet
• Energy Metabolism (drug effects)
• Insulin (blood)
• Insulin Resistance
• Isomerism
• Linoleic Acids (administration & dosage, pharmacology)
• Lipids (blood)
• Liver X Receptors
• Mice
• Orphan Nuclear Receptors
• Receptors, Cytoplasmic and Nuclear (metabolism)
• Sterol Regulatory Element Binding Protein 1
• Structure-Activity Relationship
• Transcription Factors (metabolism)
• Triglycerides (blood)
• Weight Loss (drug effects)