Hindawi Publishing Corporation Journal of Lipids Volume 2013, Article ID 890343, 16 pages http://dx.doi.org/10.1155/2013/890343 Research Article Trans-10, cis 12-Conjugated Linoleic Acid-Induced Milk Fat Depression Is Associated with Inhibition of PPAR Signaling and Inflammation in Murine Mammary Tissue Anil K. G. Kadegowda, 1 M. Jawad Khan, 2 Liliana S. Piperova, 1 Beverly B. Teter, 1 Sandra L. Rodriguez-Zas, 2 Richard A. Erdman, 1 and Juan J. Loor 2 1 Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA 2 Mammalian NutriPhysioGenomics, Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA Correspondence should be addressed to Juan J. Loor; jloor@illinois.edu Received 24 November 2012; Accepted 18 March 2013 Academic Editor: Angel Catala Copyright © 2013 Anil K. G. Kadegowda et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Exogenous trans-10, cis-12-CLA (CLA) reduces lipid synthesis in murine adipose and mammary (MG) tissues. However, genomewide alterations in MG and liver (LIV) associated with dietary CLA during lactation remain unknown. We fed mice ( = 5/diet) control or control + trans-10, cis-12-CLA (37 mg/day) between d 6 and d 10 postpartum. he 35,302 annotated murine exonic evidence-based oligo (MEEBO) microarray and quantitative RT-PCR were used for transcript proiling. Milk fat concentration was 44% lower on d 10 versus d 6 due to CLA. he CLA diet resulted in diferential expression of 1,496 genes. Bioinformatics analyses underscored that a major efect of CLA on MG encompassed alterations in cellular signaling pathways and phospholipid species biosynthesis. Dietary CLA induced genes related to ER stress (Xbp1), apoptosis (Bcl2), and inlammation (Orm1, Saa2, and Cp). It also induced marked inhibition of PPAR signaling, including downregulation of Pparg and Srebf1 and several lipogenic target genes (Scd, Fasn, and Gpam). In LIV, CLA induced hepatic steatosis probably through perturbations in the mitochondrial functions and induction of ER stress. Overall, results from this study underscored the role of PPAR signaling on mammary lipogenic target regulation. he proinlammatory efect due to CLA could be related to inhibition of PPAR signaling. 1. Introduction Dietary nutrients inluence the quantity and composition of milk during lactation. Speciically, dietary lipids regulate milk lipid synthesis and milk fatty acid composition in diferent species of animals. Recently we showed that trans fatty acids (FA) and, in particular, trans-containing conjugated linoleic acid (CLA) isomers regulate murine mammary lipid metabo- lism to diferent extents [1]. CLA isomers are the positional and geometric isomers of linoleic acid, an 18-carbon FA with two double bonds. he conjugated double bonds in the CLA are responsible for their biological and biochemical activities. Of the diferent CLA isomers, the role of trans-10, cis-12-CLA in decreasing milk fat synthesis is well established. he efects of dietary trans-10, cis-12-CLA on lipid metab- olism in adipose and liver have been examined previously [2, 3]. Gene expression proiling studies in rodent adipose [2, 4], liver [5–7], and macrophages [8] have been conducted to help elucidate the molecular mechanisms elicited by trans-10, cis-12-CLA. In adipose and liver, trans-10, cis-12-CLA reduces adipogenesis, increases hepatic steatosis, and leads to insulin resistance, hyperinsulinemia, and inlammation [3, 9]. Stud- ies on the efects of trans-10, cis-12-CLA in the mammary tissue of rodents and cows have largely focused on the changes pertaining to lipid metabolism. However, in vitro cell culture and in vivo studies have reported induction of mam- mary epithelial cell apoptosis at supraphysiological doses of CLA [10, 11].