Short-term feed restriction induces inflammation and an antioxidant response via cystathionine-β-synthase and glutathione peroxidases in ruminal epithelium from Angus steers

Decreased intake is induced by stressors such as parturition, transportation, dietary transitions, and disease. An important function of one-carbon metabolism (OCM) is to produce the antioxidant glutathione to help reduce oxidative stress. Although various components of OCM are expressed in the bovine rumen and small intestine, the relationship between reduced feed intake, OCM, and antioxidant mechanisms in gut tissues is unknown. This study aimed to assess alterations in immune and antioxidant pathways in ruminal epithelium due to acute feed restriction (FR). Seven group-housed ruminally cannulated Angus steers (663 +/- 73 kg body weight, 2 yr old) had ad libitum access to a finishing diet (dry-rolled corn, corn silage, modified wet distiller's grains) during 15 d of a pre-FR period (PRE). Subsequently, steers were moved to a metabolism barn with tie stalls and individually fed at 25% of estimated intake in PRE for 3 d (FR period, FRP). This was followed by 15 d of recovery (POST) during which steers had ad libitum access to the same diet as in PRE and FRP. Plasma and ruminal tissue biopsies were collected during each period. Plasma free fatty acid and IL1-beta concentrations were higher (P <= 0.03) in FRP than PRE or POST. The mRNA abundance of the proinflammatory genes tumor necrosis factor, toll-like receptor 2 (TLR2), and TLR4 in the ruminal epithelium peaked (P < 0.05) at FRP and remained higher at POST. These responses agreed with the higher (P < 0.05) abundance of phosphorylated (p)-MAPK (an inflammation activator) and p-EEF2 (translational repressor) in FRP than PRE and POST. Although ruminal glutathione peroxidase (GPX) enzyme activity did not increase at FRP compared with PRE and POST, protein abundance of GPX1 and GPX3 along with the antioxidant response regulator NFE2L2 were highest (P < 0.01), and the activity of cystathionine-beta synthase tended (P = 0.06) to be highest during FR. Although FR had minimal negative effects on tissue integrity-related genes (only filamin A was downregulated), it led to a systemic inflammatory response and triggered inflammation and antioxidant mechanisms within the ruminal epithelium. Thus, deploying anti-inflammatory and antioxidant mechanisms via molecules that feed into OCM (e.g., dietary methyl donors such as methionine, choline, betaine, and folate) could potentially counteract the stressors associated with FR. Heat stress, changing pens, transportation, and disease are stressors that often decrease feed intake. Undernutrition leads to physiological adaptations of which fat depot mobilization is especially important due to the effects of fatty acids on cell function including increased oxidative stress and inflammation. Ruminally cannulated Angus steers undergoing a 3-d feed restriction (FR) were used for ruminal papillae biopsies before, during, and after FR. Although mRNA abundance of most tissue integrity-related genes was not affected, tissue mRNA and protein abundance data revealed an inflammatory response and a more pronounced antioxidant response during FR. The latter was particularly evident by the marked upregulation of glutathione peroxidases and the activity of cystathionine beta-synthase responsible for glutathione synthesis. Future studies should address the role of nutrients feeding into OCM and their potential to induce antioxidant responses.