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Diabetes 51:2037-2044, 2002
© 2002 by the American Diabetes Association, Inc.

Isomer-Dependent Metabolic Effects of Conjugated Linoleic Acid

Insights From Molecular Markers Sterol Regulatory Element-Binding Protein-1c and LXR{alpha}

Helen M. Roche1, Enda Noone1, Ciaran Sewter2, Siobhan Mc Bennett3, David Savage2, Michael J. Gibney1, Stephen O’Rahilly2, and Antonio J. Vidal-Puig2

1 Molecular Nutrition, Department of Clinical Medicine, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin, Ireland
2 Department of Clinical Biochemistry and Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge, U.K.
3 Department of Physiology, Trinity College Dublin, Dublin, Ireland

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 LXR{alpha} (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 LXR{alpha} expression.


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