Isomer-Dependent Metabolic Effects of Conjugated Linoleic Acid
Insights From Molecular Markers Sterol Regulatory Element-Binding Protein-1c and LXRα
- Helen M. Roche1,
- Enda Noone1,
- Ciaran Sewter2,
- Siobhan Mc Bennett3,
- David Savage2,
- Michael J. Gibney1,
- Stephen O’Rahilly2 and
- Antonio J. Vidal-Puig2
- 1Molecular Nutrition, Department of Clinical Medicine, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin, Ireland
- 2Department of Clinical Biochemistry and Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge, U.K.
- 3Department 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 LXRα (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 α (TNF-α) mRNA (P = 0.012). Recombinant TNF-α 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 LXRα expression.
Address correspondence and reprint requests to Helen M. Roche, Department of Clinical Medicine, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin 8, Ireland. E-mail:.
Received for publication 22 November 2001 and accepted in revised form 15 March 2002.
BAT, brown adipose tissue; CLA, conjugated linoleic acid; DTT, dithiothreitol; FBS, fetal bovine serum; NEFA, nonesterified fatty acid; PUFA, polyunsaturated fatty acid; SREBP, sterol regulatory element-binding protein; TAG, triacylglycerol; TNF-α, tumor necrosis factor α; WAT, white adipose tissue.