GSE160502
Effect of over-conditioning on the hepatic global gene expression pattern of dairy cows at the end of pregnancy
Over-conditioning is a risk factor for upregulated pre- and postpartum fat mobilization. Therefore, we hypothesized that over-conditioning at the end of pregnancy leads to the accumulation of lipids in the liver and modifications of the hepatic gene expression pattern. The aim of this study was to evaluate the effect of over- versus normal-conditioning on the hepatic transcriptomic profile of dairy cows at the end of pregnancy. Ten dry multiparous Holstein cows were euthanized two weeks before expected calving. Body condition score (BCS) and backfat thickness (BFT) were evaluated, and blood samples for nonesterified fatty acids (NEFA) were taken before euthanasia. After euthanasia, liver biopsy samples were collected for further assessment of total lipids and RNA sequencing. Five cows were classified as normal-conditioned (BCS = 2.5–3.5) and five as over-conditioned (BCS = 3.75–5). Regression models confirmed that normal-conditioned cows had lower BCS [3.17 ± 0.10 (least square mean ± SE)], BFT (1.29 ± 0.29 cm), and serum NEFA (0.16 ± 0.04 mmol/L) in comparison to over-conditioned cows (4.35 ± 0.21, 3.14 ± 0.43 cm, and 0.38 ± 0.07 mmol/L for BCS, BFT, and NEFA, respectively). Total liver lipid percentage tended to be lower in normal- than over-conditioned cows (4.63 ± 0.40% and 6.06 ± 0.44%, respectively). In comparison to the mean liver lipid percentage of the normal and over conditioned cows, one over-conditioned cow had a relatively low (5.21%) and one normal-conditioned cow had a relatively high (6.07%) liver lipid percentage. Differentially expressed genes (DEGs) analysis (edgeR quasi-likelihood method) showed that normal-conditioned presented two upregulated and five downregulated genes in comparison to over-conditioned cows. Linear discriminant analysis effects size revealed 23 DEG between normal- versus over-conditioned cows. Notably, the liver of normal-conditioned cows had upregulated genes associated with liver functionality (albumin, selenoprotein P, and insulin-like growth factor binding protein 1 and 2). On the other hand, over-conditioned cows had upregulated genes associated with the acute phase response (complement C3, hemopexin, and lipopolysaccharide-binding protein). High basal lipolysis in over-conditioned cows at the end of pregnancy increases liver lipid content and alters the hepatic gene expression pattern to a pro-inflammatory state. Overall design: Evaluation of the liver transcriptome of over- and normal-conditioned dairy cows two weeks before expected parturition