Rumen-protected methionine compared with rumen-protected choline improves immunometabolic status in dairy cows during the peripartal period

Abstract

The immunometabolic status of peripartal cows is altered due to changes in liver function, inflammation, and oxidative stress. Nutritional management during this physiological state can affect the biological components of immunometabolism. The objectives of this study were to measure concentrations of biomarkers in plasma, liver tissue, and milk, and also polymorphonuclear leukocyte function to assess the immunometabolic status of cows supplemented with rumen-protected methionine (Met) or choline (CHOL). Forty-eight multiparous Holstein cows were used in a randomized complete block design with 2×2 factorial arrangement of Met (Smartamine M, Adisseo NA, Alpharetta, GA) and CHOL (ReaShure, Balchem Inc., New Hampton, NY) level (with or without). Treatments (12 cows each) were control (CON), no Met or CHOL; CON and Met (SMA); CON and CHOL (REA); and CON and Met and CHOL (MIX). From -50 to -21d before expected calving, all cows received the same diet [1.40Mcal of net energy for lactation (NE)/kg of DM] with no Met or CHOL. From -21d to calving, cows received the same close-up diet (1.52Mcal of NE/kg of DM) and were assigned randomly to each treatment. From calving to 30d, cows were on the same postpartal diet (1.71Mcal of NE/kg of DM) and continued to receive the same treatments until 30d. The Met supplementation was adjusted daily at 0.08% DM of diet, and CHOL was supplemented at 60g/cow per day. Liver (-10, 7, 21, and 30d) and blood (-10, 4, 8, 20, and 30d) samples were harvested for biomarker analyses. Neutrophil and monocyte phagocytosis and oxidative burst were assessed at d 1, 4, 14, and 28d. The Met-supplemented cows tended to have greater plasma paraoxonase. Greater plasma albumin and IL-6 as well as a tendency for lower haptoglobin were detected in Met- but not CHOL-supplemented cows. Similarly, cows fed Met compared with CHOL had greater concentrations of total and reduced glutathione (a potent intracellular antioxidant) in liver tissue. Upon a pathogen challenge in vitro, blood polymorphonuclear leukocyte phagocytosis capacity and oxidative burst activity were greater in Met-supplemented cows. Overall, liver and blood biomarker analyses revealed favorable changes in liver function, inflammation status, and immune response in Met-supplemented cows.

Methionine supply during the periparturient period enhances insulin signaling, amino acid transporters, and mechanistic target of rapamycin pathway proteins in adipose tissue of Holstein cows

“…Recent studies feeding RPM to enhance Met supply during the periparturient period have underscored the importance of this AA for milk protein synthesis but also for synthesis of antioxidants such as glutathione (Osorio et al, 2014a;Zhou et al, 2016aZhou et al, , 2018Batistel et al, 2017bBatistel et al, , 2018. The decrease in plasma insulin after parturition is well documented (De Koster et al, 2018) and explains in part the typical surge in plasma fatty acids as detected in the cows used in this study (Batistel et al, 2018).…”

“…A state of insulin resistance (Sordillo and Raphael, 2013;De Koster et al, 2018) designed to limit glucose utilization by tissues such as adipose and muscle (Zhai et al, 2010) also characterizes the transition period. These endocrine and physiologic adaptations are now considered components of homeorhesis, allowing the mammary gland to have priority over nutrient utilization for milk synthesis (Vailati-Riboni et al, 2015;Zhou et al, 2016a). Despite the importance of insulin signaling in adipose tissue, few studies (e.g., Zachut et al, 2013) have addressed the concerted longitudinal adaptations of insulin-sensitive components including the insulin receptor (INSR), intracellular kinases (e.g., insulin receptor 1, IRS1; AKT serine/threonine kinase, AKT), glucose transporters (solute carrier family 2 member 4; SLC2A4), transcription regulators (e.g., peroxisome proliferator-activated receptor gamma, PPARG), and enzyme targets (e.g., fatty acid synthase, FASN).…”

Methionine and choline supply alter transmethylation, transsulfuration, and cytidine 5′-diphosphocholine pathways to different extents in isolated primary liver cells from dairy cows

“…Dietary Met and Chol supplementation around parturition in rumen-protected form increased milk yield and milk protein concentration (Sales et al, 2010;Osorio et al, 2013;Zhou et al, 2016c), and Met improved immunometabolic status in dairy cows during the peripartal period (Osorio et al, 2014b;Zhou et al, 2016a). Furthermore, compared with Chol, greater supply of Met resulted in increased antioxidant concentration in liver tissue in spite of lower concentration of PC (Zhou et al, 2017).…”

“…The regulation and coordination of lipid metabolism (at molecular, enzyme, and metabolite level) among adipose tissue, liver, gut, and mammary gland are key components of the adaptations to lactation . Although several recent studies have enhanced the mechanistic understanding of the role of Met and Chol in the context of the physiology of the periparturient cow (Zhou et al, 2016a(Zhou et al, ,b, 2017Zenobi et al, 2018), studying mechanistic aspects of Met and Chol metabolism in liver in vivo becomes challenging.…”

Glutathione metabolism and nuclear factor erythroid 2-like 2 (NFE2L2)-related proteins in adipose tissue are altered by supply of ethyl-cellulose rumen-protected methionine in peripartal Holstein cows

“…Glutathione (GSH) is a well-established antioxidant in cells and plays a critical role in the maintenance and regulation of the thiol-redox status (Aquilano et al, 2014). Methionine, which is one of the most-limiting AA for lactating dairy cattle, participates in one-carbon metabolism and synthesis of GSH, both of which occur primarily in the liver (Martinov et al, 2010;Zhou et al, 2016aZhou et al, , 2017. When Lys was adequate, feeding RPM to achieve a Lys: Met ratio close to 2.8:1 in the MP during the periparturient period consistently alleviated oxidative stress status and inflammation in dairy cows and improved DMI and milk yield (Osorio et al, 2014b;Batistel et al, 2017;Zhou et al, 2017).…”