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.

Highlights

  • 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)

  • Results from the principal component analysis (PCA) performed based on the rlog-transformed gene counts showed that the first two principal components accounted for 45% (PC1) and 10% (PC2) of the variance (Fig. 1)

  • The 1,256 genes upregulated in the CLA-MFD group were clustered in 1,205 Gene Ontology (GO) terms [994 in the GO biological process category (GO-BP), 95 in the GO Molecular Function category (GO-MF) and 116 in the GO Cellular Component category (GO-CC); Supplementary Table S1]

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Summary

Introduction

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). Milk fat depression (MFD) syndrome is generally characterized by a strong reduction in milk fat content without significant changes in the yield of milk or other milk components[1] This syndrome was first described in dairy cows fed highly fermentable or plant oil-containing diets, where it is primarily mediated by the rumen metabolite trans-10 cis-12 CLA2. Dairy ewes displaying trans-10 cis-12 CLA-induced MFD have been proposed as a model to examine mammary mechanisms explaining low-fat milk syndrome in cows[9]. These ewes might not be a good model to study the diet-induced MFD in ewes themselves, which is caused by marine lipid supplementation. In a study conducted in lactating sheep fed a diet supplemented with either FO or trans-10 cis-12 CLA4, similar changes were observed in the milk fat content and in the processes of de novo FA synthesis and FA uptake, www.nature.com/scientificreports/

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