Isomer-Dependent Metabolic Effects of Conjugated Linoleic Acid: Insights From Molecular Markers Sterol Regulatory Element-Binding Protein-1c and LXRα

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.