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Hepatic differential gene expression of cows clustered by postpartum metabolites: A model for susceptibility to lipid-related metabolic disorders.

R. Pralle

Events

06-22-2020

Abstract:

69
Hepatic differential gene expression of cows clustered by postpartum metabolites: A model for susceptibility to lipid-related metabolic disorders.
R. Pralle*1, W. Li2, H. White1. 1Department of Dairy Science, University of Wisconsin Madison, WI, 2Cell Wall Biology and Utilization Laboratory, USDA-ARS Madison, WI.

We propose that cows developing metabolic disorders (MD) in the absence of induction, compared with those that do not, represent groups of MD susceptibility. Our study objectives were to identify differentially expressed genes (DEG) and enriched metabolic pathways (EMP) associated with susceptibility to MD. From a larger multiparous transition cow study, the control treatment (n = 13) was clustered (K-means, R, v. 3.5.2) based on postpartum blood fatty acid, BHB, and liver triglyceride concentrations. Metabolite means within the largest 2 clusters revealed one cluster with a preferable low metabolite concentration profile (less susceptible, LS) and a cluster with disfavorably greater metabolite concentrations (MD susceptible, MS). From each cluster, 3 cows were selected for whole transcriptome RNaseq of liver tissue collected at +1 and +14 d relative to calving (DRTC). Alignment of reads to the Bos taurus genome, DEG analysis between LS and MS clusters within DRTC, and EMP analysis were done using STAR (v.2.5.2b), Cufflinks (Cuffdiff, v.2.2.1), and DAVID (v.6.8), respectively. DEG and EMP were considered significant and tendencies when P ≤ 0.05 and 0.05 < P ≤ 0.10, respectively, after FDR-adjustment. Within +1 DRTC, 102 significant and 35 DEG tendencies were observed. Unique genes with an absolute fold change (FC) > 5.2 were REC8, IFI6, and IFI27. There were 175 significant and 48 DEG tendencies on +14 DRTC; unique genes (FC > 8) included MEDAG, FABP4, HP, and SAA2. Between DRTC, 44 DEG with P ≤ 0.10 were shared, including ULBP27, SFRP2, and PDYN. Unique +1 DRTC EMP included protein processing by the endoplasmic reticulum, RIG-I-like receptor signaling pathway, and phagosome. Protein digestion and absorption, regulation of lipolysis in adipocytes, and PPAR signaling pathway were unique EMP to +14 DRTC. Four EMP were shared between DRTC including glutathione metabolism and cytochrome P450 metabolism of drugs and xenobiotics. These results suggest hepatic transcriptome features of MD susceptibility relate to immunity, inflammation, regulation of lipid metabolism, and P450-mediated metabolism.

Keywords: ketosis, fatty liver, RNAseq.