Conjugated linoleic acid (CLA)-induced milk fat depression: application of RNA-Seq technology to elucidate mammary gene regulation in dairy ewes

Abstract

Milk fat depression (MFD) is characterized by a reduction in the content of milk fat, presumably caused by the anti-lipogenic effects of rumen biohydrogenation intermediates, such as trans-10 cis-12 conjugated linoleic acid (CLA). In this study, RNA-Seq technology was used to help elucidate the mammary responses involved in CLA-induced MFD in lactating ewes. To this end, we compared the milk somatic cell transcriptome of ewes suffering from CLA-induced MFD with control ewes (i.e., those without MFD), as well as with ewes fed a diet supplemented with fish oil (FO-MFD) that we previously reported affects the mammary transcriptome. In the differential expression analysis between CLA-MFD and controls, we identified 1,524 differentially expressed genes (DEGs), whereas 653 were detected between CLA- and FO-MFD groups. Although this article focuses on lipid metabolism, CLA affected the expression of many genes related to other biological processes, especially immunity. Among the 55 genes shared by both MFD conditions, some genes linked to fatty acid synthesis, such as ACACA, AACS, ACSS2, or ACSS3, were downregulated. In addition, this study provides a list of candidate genes that are not usually considered in the nutrigenomics of MFD but that may act as key regulators of this syndrome in dairy ewes.

Nutritional Regulation of Mammary Gland Development and Milk Synthesis in Animal Models and Dairy Species

“…Indeed, mammary epithelial cells are exfoliated from the mammary epithelium and are an alternative sample to study MG expression [ 146 ]. Using RNA-seq, a comparison between two diets inducing milk fat depression (CLA vs. fish oil diets) showed 653 differentially expressed genes (DEGs) in milk somatic cells according to the supplementation, whereas fish oil supplementation, compared to the control diet, altered the expression of 237 genes [ 147 ]. Among the 55 genes communally modulated by both milk fat depression diets compared to the control diets, ACACA , AACS , ACSS2 , ACSS3, and FADS2 , which are involved in FA synthesis, were downregulated, which is in line with the milk fat depression.…”

The Effect of CLA-Rich Isomerized Poppy Seed Oil on the Fat Level and Fatty Acid Profile of Cow and Sheep Milk

“…Low-fat milk syndrome, more commonly referred to as milk fat depression (MFD), is a state that naturally occurs in dairy production when animals are fed highly fermentable diets or dietary plant or fish oil supplements [35,36]. As a result of disturbances in the rumen biohydrogenation process, FAs are produced as intermediate products, which are strong inhibitors of milk fat synthesis [37,38]. The MFD mechanism focuses on the mammary gland and includes a coordinated reduction of mRNA genes of key enzymes associated with all aspects of milk fat synthesis [38,39].…”

“…As a result of disturbances in the rumen biohydrogenation process, FAs are produced as intermediate products, which are strong inhibitors of milk fat synthesis [37,38]. The MFD mechanism focuses on the mammary gland and includes a coordinated reduction of mRNA genes of key enzymes associated with all aspects of milk fat synthesis [38,39]. These processes include de novo synthesis of FAs, collection and transport of previously produced FAs, and denaturation and incorporation into triglycerides (TGs).…”

“…These processes include de novo synthesis of FAs, collection and transport of previously produced FAs, and denaturation and incorporation into triglycerides (TGs). The trans-10,cis-12 CLA isomer has been proven to be a potential nutritional tool to manipulate milk fat synthesis and FA profiles in lactating animals [17,38,40]. The activity of desaturase ∆ 9 , responsible for fat synthesis in the mammary gland, was probably also inhibited by TVA formed from CLA during ruminal transformations [41].…”

Gene Expression Profiling and Biofunction Analysis of HepG2 Cells Targeted by Crocetin

“…Therefore, changing the dietary composition and proportion of farm animals could improve the nutritional value of meat products [13][14][15]. Suarez-Vega et al [16] used the RNA-seq technique to study the MED-related mammary responses induced by CLA in breast milk, and compared the transcriptome data of mammary cells in ewes with the CLA-induced MFD group, the non-MED group, and the FO-MFD group, and identified the core genes involved in the downregulation of fatty acid synthesis in CLA-MFD and FO-MFD. Today, RNA-seq remains the preferred method of analysis for transcriptomes, and nutritionists are able to use transcriptome data to develop a framework for improving dietary composition and novel functional foods as a way to promote human health.…”