Trans-10,cis12-Conjugated Linoleic Acid-Induced Milk Fat Depression Is Associated with Inhibition of PPARγSignaling and Inflammation in Murine Mammary Tissue

Abstract

Exogenoustrans-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 (n=5/diet) control or control + trans-10,cis-12-CLA (37 mg/day) between d 6 and d 10 postpartum. The 35,302 annotated murine exonic evidence-based oligo (MEEBO) microarray and quantitative RT-PCR were used for transcript profiling. Milk fat concentration was 44% lower on d 10 versus d 6 due to CLA. The CLA diet resulted in differential expression of 1,496 genes. Bioinformatics analyses underscored that a major effect 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 inflammation (Orm1,Saa2, andCp). It also induced marked inhibition of PPARγsignaling, including downregulation ofPpargandSrebf1and several lipogenic target genes (Scd,Fasn, andGpam). 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 PPARγsignaling on mammary lipogenic target regulation. The proinflammatory effect due to CLA could be related to inhibition of PPARγsignaling.