Liver fat content and lipid metabolism in dairy cows during early lactation and during a mid-lactation feed restriction

During the transition period, the lipid metabolism of dairy cows is markedly affected by energy status. Fatty liver is one of the main health disorders after parturition. The aim of this study was to evaluate the effects of a negative energy balance (NEB) at 2 stages in lactation [NEB at the onset of lactation postpartum (p.p.) and a deliberately induced NEB by feed restriction near 100 d in milk] on liver triglyceride content and parameters of lipid metabolism in plasma and liver based on mRNA abundance of associated genes. Fifty multiparous dairy cows were studied from wk 3 antepartum to approximately wk 17 p.p. in 2 periods. According to their energy balance in period 1 (parturition to wk 12 p.p.), cows were allocated to a control (CON; n=25) or a restriction group (RES; 70% of energy requirements; n=25) for 3 wk in mid lactation starting at around 100 d in milk (period 2). Liver triglyceride (TG) content, plasma nonesterified fatty acids (NEFA), and β-hydroxybutyrate were highest in wk 1 p.p. and decreased thereafter. During period 2, feed restriction did not affect liver TG and β-hydroxybutyrate concentration, whereas NEFA concentration was increased in RES cows as compared with CON cows. Hepatic mRNA abundances of tumor necrosis factor α, ATP citrate lyase, mitochondrial glycerol-3-phosphate acyltransferase, and glycerol-3-phosphate dehydrogenase 2 were not altered by lactational and energy status during both experimental periods. The expression of fatty acid synthase was higher in period 2 compared with period 1, but did not differ between RES and CON groups. The mRNA abundance of acetyl-coenzyme A-carboxylase showed a tendency toward higher expression during period 2 compared with period 1. The solute carrier family 27 (fatty acid transporter), member 1 (SLC27A1) was upregulated in wk 1 p.p. and also during feed restriction in RES cows. In conclusion, the present study shows that a NEB has different effects on hepatic lipid metabolism and TG concentration in the liver of dairy cows at early and later lactation. Therefore, the homeorhetic adaptations during the periparturient period trigger excessive responses in metabolism, whereas during the homeostatic control of endocrine and metabolic systems after established lactation, as during the period of feed restriction in the present study, organs are well adapted to metabolic and environmental changes

Molecular networks of insulin signaling and amino acid metabolism in subcutaneous adipose tissue are altered by body condition in periparturient Holstein cows

[EN] Peripartal cows mobilize not only body fat but also body protein to satisfy their energy requirements. The objective of this study was to determine the effect of prepartum BCS on blood biomarkers related to energy and nitrogen metabolism, and mRNA and protein abundance associated with AA metabolism and insulin signaling in subcutaneous adipose tissue (SAT) in peripartal cows. Twenty-two multiparous Holstein cows were retrospectively classified into a high BCS (HBCS; n = 11, BCS >= 3.5) or normal BCS (NBCS; n = 11, BCS <= 3.17) group at d 28 before expected parturition. Cows were fed the same diet as a total mixed ration before parturition and were fed the same lactation diet postpartum. Blood samples collected at -10, 7, 15, and 30 d relative to parturition were used for analyses of biomarkers associated with energy and nitrogen metabolism. Biopsies of SAT harvested at -15, 7, and 30 d relative to parturition were used for mRNA (real timePCR) and protein abundance (Western blotting) assays. Data were subjected to ANOVA using the MIXED procedure of SAS (v. 9.4; SAS institute Inc., Cary, NC), with P <= 0.05 being the threshold for significance. Cows in HBCS had greater overall plasma nonesterified fatty acid concentrations, due to marked increases at 7 and 15 d postpartum. This response was similar (BCS x Day effect) to protein abundance of phosphorylated (p) protein kinase B (p-AKT), the insulin-induced glucose transporter (SLC2A4), and the sodium-coupled neutral AA transporter (SLC38A1). Abundance of these proteins was lower at -15 d compared with NBCS cows, and either increased (SLC2A4, SLC38A1) or did not change (p-AKT) at 7 d postpartum in IIBCS. Unlike protein abundance, however, overall mRNA abundances of the high-affinity cationic (SLC7A1), proton-coupled (SLC96A1), and sodium-coupled amino acid transporters (SLC,98,42) were greater in IIBCS than NBCS cows, due to upregulation in the postpartum phase. Those responses were similar to protein abundance of p-mTOR, which increased (BCS x Day effect) at 7 d in HBCS compared with NBCS cows. mRNA abundance of argininosuccinate lyase (ASL) and arginase 1 (ARG1) also was greater overall in HBCS cows. Together, these responses suggested impaired insulin signaling, coupled with greater postpartum AA transport rate and urea cycle activity in SAT of HBCS cows. An in vitro study using adipocyte and macrophage cocultures stimulated with various concentrations of fatty acids could provide some insights into the role of immune cells in modulating adipose tissue immunometabolic status, including insulin resistance and AA metabolism.Y. Liang is a recipient of a doctoral fellowship from the China Scholarship Council (CSC, Beijing, China) to perform his PhD studies at the University of Illinois (Urbana). A. S. Alharthi received a fellowship from King Saud University (Riyadh, Saudi Arabia) to perform his PhD studies at the University of Illinois (Urbana). A. A. Elolimy was recipient of a fellowship from the Higher Education Ministry (Cairo, Egypt) to perform his PhD studies at the University of Illinois (Urbana). We thank Perdue AgriBusiness (Salisbury, MD) for the donation of ProvAAL2 AADvantage during the course of the experiment. The authors declare no conflicts of interest.Liang, Y.; Alharthi, A.; Elolimy, A.; Bucktrout, R.; Lopreiato, V.; Cortes, I.; Xu, C.... (2020). Molecular networks of insulin signaling and amino acid metabolism in subcutaneous adipose tissue are altered by body condition in periparturient Holstein cows. 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Transcriptional regulation of lipid metabolism and inflammation in transition dairy goats by fish oil and stearate

To better understand the interaction between saturated or unsaturated fatty acids and its effect on expression of genes involved in subcutaneous adipose tissue metabolism, 23 second parity alpine dairy goats were enrolled in the experiment and fed either a non fat-supplemented basal diet (C; n=8), the basal diet supplemented with stearic acid (ST; n=7) or the basal diet supplemented with fish oil (FO; n=8). 30g/head/d supplemental fatty acids during the dry period and 50g/head/d during lactation were delivered starting one week before parturition up to 21 days in milk. Subcutaneous adipose tissue samples were harvested at day -7, 7 and 21 relative to kidding and mRNA levels of genes involved in inflammation were measured via qPCR. Data were analyzed using the MIXED procedure of SAS. No significant effects for treatment were observed, however eight genes were significant for time. HP and SAA3 expression peaked at day 7 postpartum, to then return at prepartum level around 21 d relative to kidding, while IL8, IL10, and IL18 expression constantly increased along the transition period. Vice versa, expression of IL1\u3b2, IL6R, and RXRA decreased in response to kidding, with a subsequent increase at day 21. The obtained results led us to hypothesize that goats face a postponed lipomobilization after kidding, probably related to their reduced production. The next step will involve the analysis of miRNA related to immune cell infiltration, adipocyte inflammation and lipolysis and positive regulation of adipogenesis to better understand the complex network of lipid metabolism in periparturient goats

Body condition alters glutathione and nuclear factor erythroid 2-like 2 (NFE2L2)-related antioxidant network abundance in subcutaneous adipose tissue of periparturient Holstein cows

[EN] Dairy cows with high body condition score (BCS) in late prepartum are more susceptible to oxidative stress (OS). Nuclear factor erythroid 2-like 2 (NFE2L2) is a major antioxidant transcription factor. We investigated the effect of precalving BCS on blood biomarkers associated with OS, inflammation, and liver function, along with mRNA and protein abundance of targets related to NFE2L2 and glutathione (GSH) metabolism in s.c. adipose tissue (SAT) of periparturient dairy cows. Twenty-two multiparous Holstein cows were retrospectively classified into a high BCS (HBCS; n = 11, BCS ¿3.5) or normal BCS (NBCS; n = 11, BCS ¿3.17) on d 28 before parturition. Cows were fed a corn silage- and wheat straw-based total mixed ration during late prepartum, and a corn silage- and alfalfa hay-based total mixed ration postpartum. Blood samples obtained at ¿10, 7, 15, and 30 d relative to parturition were used for analyses of biomarkers associated with inflammation, including albumin, ceruloplasmin, haptoglobin, and myeloperoxidase, as well as OS, including ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), and ß-carotene. Adipose biopsies harvested at ¿15, 7, and 30 d relative to parturition were analyzed for mRNA (real-time quantitative PCR) and protein abundance (Western blotting) of targets associated with the antioxidant transcription regulator nuclear factor, NFE2L2, and GSH metabolism pathway. In addition, concentrations of GSH, ROS and malondialdehyde were measured. High BCS cows had lower prepartum dry matter intake expressed as a percentage of body weight along with greater BCS loss between ¿4 and 4 wk relative to parturition. Plasma concentrations of ROS and FRAP increased after parturition regardless of treatment. Compared with NBCS, HBCS cows had greater concentrations of FRAP at d 7 postpartum, which coincided with peak values in those cows. In addition, NBCS cows experienced a marked decrease in plasma ROS after d 7 postpartum, while HBCS cows maintained a constant concentration by d 30 postpartum. Overall, ROS concentrations in SAT were greater in HBCS cows. However, overall mRNA abundance of NFE2L2 was lower and cullin 3 (CUL3), a negative regulator of NFE2L2, was greater in HBCS cows. Although HBCS cows had greater overall total protein abundance of NFE2L2 in SAT, ratio of phosphorylated NFE2L2 to total NFE2L2 was lower, suggesting a decrease in the activity of this antioxidant system. Overall, mRNA abundance of the GSH metabolism-related genes glutathione reductase (GSR), glutathione peroxidase 1 (GPX1), and transaldolase 1 (TALDO1), along with protein abundance of glutathione S-transferase mu 1 (GSTM1), were greater in HBCS cows. Data suggest that HBCS cows might experience greater systemic OS after parturition, while increased abundance of mRNA and protein components of the GSH metabolism pathway in SAT might help alleviate tissue oxidant status. Data underscored the importance of antioxidant mechanisms at the tissue level. Thus, targeting these pathways in SAT during the periparturient period via nutrition might help control tissue remodeling while allowing optimal performance.Y. Liang is a recipient of a doctoral fellowship from China Scholarship Council (CSC, Beijing, China). A. S. Alharthi received a fellowship from King Saud University to perform his PhD studies at the University of Illinois (Urbana). A. A. Elolimy was recipient of a fellowship from Higher Education Ministry, Egypt to perform his Ph.D. studies at the University of Illinois (Urbana). We thank Perdue AgriBusiness (Salisbury, MD) for the donation of ProvAAL2 AADvantage during the course of the experiment. The authors have not stated any conflicts of interest.Liang, Y.; Alharthi, A.; Bucktrout, R.; Elolimy, A.; Lopreiato, V.; Martinez-Cortes, I.; Xu, C.... (2020). Body condition alters glutathione and nuclear factor erythroid 2-like 2 (NFE2L2)-related antioxidant network abundance in subcutaneous adipose tissue of periparturient Holstein cows. Journal of Dairy Science. 103(7):6439-6453. https://doi.org/10.3168/jds.2019-17813S643964531037Alharthi, A., Zhou, Z., Lopreiato, V., Trevisi, E., & Loor, J. J. (2018). Body condition score prior to parturition is associated with plasma and adipose tissue biomarkers of lipid metabolism and inflammation in Holstein cows. Journal of Animal Science and Biotechnology, 9(1). doi:10.1186/s40104-017-0221-1Aquilano, K., Baldelli, S., & Ciriolo, M. R. (2014). Glutathione: new roles in redox signaling for an old antioxidant. 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Development of a dynamic energy-partitioning model for enteric methane emissions and milk production in goats using energy balance data from indirect calorimetry studies

[EN] The main objective of this study was to develop a dynamic energy balance model for dairy goats to describe and quantify energy partitioning between energy used for work (milk) and that lost to the environment. Increasing worldwide concerns regarding livestock contribution to global warming underscore the importance of improving energy efficiency utilization in dairy goats by reducing energy losses in feces, urine and methane (CH4). A dynamic model of CH(4)emissions from experimental energy balance data in goats is proposed and parameterized (n= 48 individual animal observations). The model includes DM intake, NDF and lipid content of the diet as explanatory variables for CH(4)emissions. An additional data set (n= 122 individual animals) from eight energy balance experiments was used to evaluate the model. The model adequately (root MS prediction error,RMSPE) represented energy in milk (E-milk;RMSPE = 5.6%), heat production (HP;RMSPE = 4.3%) and CH(4)emissions (E-CH4; RMSPE = 11.9%). Residual analysis indicated that most of the prediction errors were due to unexplained variations with small mean and slope bias. Some mean bias was detected for HP (1.12%) and E-CH4(1.27%) but was around zero for E-milk (0.14%). The slope bias was zero for HP (0.01%) and close to zero for E-milk (0.10%) and E-CH4(0.22%). Random bias was >98% for E-CH4, HP and E-milk, indicating non-systematic errors and that mechanisms in the model are properly represented. As predicted energy increased, the model tended to underpredict E-CH(4)and E-milk. The model is a first step toward a mechanistic description of nutrient use by goats and is useful as a research tool for investigating energy partitioning during lactation. 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