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Biochemical, Molecular, and Genetic Mechanisms

Conjugated Linoleic Acid Alters Global Gene Expression in Human Intestinal-Like Caco-2 Cells in an Isomer-Specific Manner^1–3,

⁴ Department of Food and Nutritional Sciences, and Department of Medicine, University College, Cork, Ireland; ⁵ Nutrition, Metabolism and Nutrigenomics Group, Division of Human Nutrition, Wageningen University, Wageningen 6700 EV, The Netherlands; and ⁶ Bioinformatics and Genomics Unit, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy

^* To whom correspondence should be addressed. E-mail: k.cashman{at}ucc.ie.

Conjugated linoleic acid (CLA) exhibits isomer-specific effects on transepithelial calcium (Ca) transport as well as on cell growth in human intestinal-like Caco-2 cells. However, the molecular mechanisms of action are still unclear. Therefore, this study used a transcriptomic approach to help elucidate the molecular mechanisms underlying such isomer-specific effects. Caco-2 cells were treated with 80 µmol/L linoleic acid (control), 80 µmol/L trans-10, cis-12 CLA, or 80 µmol/L cis-9, trans-11 CLA for 12 d. Ca transport was measured radio-isotopically. RNA was isolated from the cells, labeled, and hybridized to the Affymetrix U133 2.0 Plus arrays (n = 3). Data and functional analysis was preformed using Bioconductor. Using a minimum fold-change criterion of 1.6 and a false discovery rate criterion of P-value 0.05, trans-10, cis-12 CLA altered the expression of 918 genes, whereas, cis-9, trans-11 CLA had no effect on gene expression. Gene ontology analysis revealed that trans-10, cis-12 CLA strongly modulated a number of processes inherently related to carcinogenesis, such as cell cycle, cell proliferation, and DNA metabolism. Trans-10, cis-12 CLA, but not cis-9, trans-11 CLA, increased transepithelial Ca transport in Caco-2 cells, which corresponded to changes in molecular mediators of paracellular (including claudin 2 and 4) and transcellular (calbindin D₉k and vitamin D receptor) Ca transport. This microarray-based study highlighted a number of gene expression patterns of relevance to 2 important intestinal processes (carcinogenesis and Ca transport), which were modulated by trans-10, cis-12 CLA. These may help our mechanistic understanding of the role of CLA in promoting gut function and health.

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