Grain challenge affects systemic and hepatic molecular biomarkers of inflammation, stress, and metabolic responses to a greater extent in Holstein than Jersey cows

Abstract

Long-term feeding of high-grain diets to dairy cows often results in systemic inflammation characterized by alterations in acute-phase proteins and other biomarkers, both in plasma and immune-responsive tissues like the liver. The molecular and systemic changes that characterize an acute grain feeding challenge remain unclear. The current study involved 6 Holstein and 6 Jersey cows in a replicated 2 × 2 Latin square. Periods (10 d) were divided into 4 stages (S): S1, d 1 to 3, served as baseline with total mixed ration (TMR) ad libitum; S2, d 4, served as restricted feeding, with cows offered 50% of the average daily intake observed in S1; S3, d 5, a grain challenge was performed, in which cows were fed a TMR ad libitum without (CON) or with an additional pellet wheat-barley (1:1; HIG) at 20% of dry matter intake top-dressed onto the TMR; S4, d 6 to 10, served as recovery during which cows were allowed ad libitum access to the TMR. Among the 28 biomarkers analyzed in blood 12 h after grain challenge on d 5, the concentrations of fatty acids and bilirubin increased in HIG Holstein but not Jersey cows. In Holsteins, feeding HIG also increased total protein and albumin while decreasing ceruloplasmin, myeloperoxidase, and alkaline phosphatase concentrations. At the molecular level, hepatic genes associated with inflammation (IL1B, IL6, TNF, TLR4, MYD88, and NFKB1) were upregulated in Holstein cows fed HIG versus CON. Despite such response, expression of the acute-phase proteins SAA and HP in Holsteins fed HIG compared with CON was markedly downregulated. In Holsteins fed HIG versus CON, the marked downregulation of SCD, ELOVL6, and MTTP along with upregulated CPT1A, ACOX1, and APOA5 indicated alterations in fatty acid and lipoprotein metabolism during grain challenge. Genes related to ketogenesis (HMGCS2 and ACAT1) were upregulated in Jerseys, and gluconeogenic genes (PDK4 and PCK1) were upregulated in Holstein cows fed HIG, suggesting alterations in ketone body and glucose production. Expression of phosphorylated p70S6K1, RPS6, and 4EBP1 proteins, as well as total mechanistic target of rapamycin (mTOR) protein, decreased in Holsteins fed HIG, whereas phosphorylated mTOR and 4EBP1 proteins increased in Jerseys fed HIG. From a metabolic and inflammatory biomarker standpoint, data indicate that Jersey cows better tolerated the acute grain challenge. Alterations in mTOR signaling proteins in both Jerseys and Holsteins fed HIG suggest a potential role for exogenous AA in the hepatic adaptations to grain challenge. It remains to be determined if these acute responses to a grain challenge can elicit long-term liver dysfunction, which could negatively affect welfare of the cow.

Aluminosilicate clay improves production responses and reduces inflammation during an aflatoxin challenge in lactating Holstein cows

“…Activation of MTOR has been associated with increased lipogenesis Liu et al, 2016). Xu et al (2017) indicated that an upregulation in MTOR in Jersey cows fed high-grain diets as a challenge could be responsible for increased hepatic lipogenesis. In the current study, downregulation of MTOR for cows in POS could explain the decrease in serum cholesterol for this treatment.…”

“…Similar results were observed in Pate and Cardoso (2018), where hepatic NFKB1 expression was greater in cows challenged with AF compared with cows without AF challenge. Additionally, Xu et al (2017) reported increased hepatic NFKB1 expression when a grain challenge was fed to Holstein cows. Increased NFKB1 expression has been shown to regulate other inflammatory genes, such as TNFA and IL6, which are proinflammatory cytokines (Baker et al, 2011).…”

Review: Enhancing gastrointestinal health in dairy cows

“…Beyond the well-established effects of ruminal acidosis on epithelial integrity and molecular responses, there has been interest in using genome-enabled technologies for evaluating the post-ruminal effect of acidosis. Examples include work with mRNA and/or protein expression in the liver (Chang et al, 2015;Xu et al, 2017), white blood cells (Stefanska et al, 2017) and mammary gland (Jin et al, 2016;. In regards to the liver, acute (1 day) or chronic (10 weeks) ruminal acidosis in Holstein cows induced by feeding a high-grain diet causes upregulation of inflammatory mediators (Chang et al, 2015;Xu et al, 2017).…”

“…Examples include work with mRNA and/or protein expression in the liver (Chang et al, 2015;Xu et al, 2017), white blood cells (Stefanska et al, 2017) and mammary gland (Jin et al, 2016;. In regards to the liver, acute (1 day) or chronic (10 weeks) ruminal acidosis in Holstein cows induced by feeding a high-grain diet causes upregulation of inflammatory mediators (Chang et al, 2015;Xu et al, 2017). Hence, the pro-inflammatory response to acidosis is not unique to rumen epithelium and even extends to circulating white blood cells (Stefanska et al, 2017) and the mammary gland .…”

“…Recent efforts to better understand the response of the liver to grain challenges have gone beyond the inflammatory response. For instance, an acute grain challenge after a 1 day of feed restriction downregulated genes encoding metabolic enzymes associated with elongation (ELOVL fatty acid elongase 6) and desaturation (stearoyl-CoA desaturase) of long-chain fatty acids but upregulated gluconeogenic genes (pyruvate dehydrogenase kinase 4; phosphoenolpyruvate carboxykinase 1; Xu et al, 2017). From a mechanistic standpoint, blocking elongation and desaturation could lead to ceramide production and trigger inflammation (Kasumov et al, 2015).…”