Acute interstitial pneumonia and the biology of 3-methylindole in feedlot cattle.

Acute interstitial pneumonia (AIP) of cattle has been recognized for many decades. While the pathogenesis and risk factors for this condition in pastured cattle are relatively well characterized, there remains a poor understanding of the disease as it occurs in intensively fed cattle such as in beef feedlots. Specifically, in pastured cattle, AIP results from excessive ruminal production of the pneumotoxicant 3-methylindole (3-MI). In feedlot cattle, the evidence to substantiate the role of 3-MI is comparatively deficient and further investigations into the cause, pathogenesis, and control are sorely needed. This review highlights our current understanding of AIP with a focus on the disease as it occurs in feedlot cattle. Additionally, it illustrates the need for further work in understanding the specific animal factors (e.g. the ruminal microbiome, and the role of concurrent diseases), management factors (e.g. animal stocking and vaccination protocols), and dietary factors (e.g. dietary supplements) that may impact the development of AIP and which are relatively unique to the feedlot setting. All stakeholders in the beef industry stand to benefit from a greater understanding of what remains a pressing yet poorly understood issue in beef production.

Vitamin E in New-Generation Lipid Emulsions Protects Against Parenteral Nutrition-Associated Liver Disease in Parenteral Nutrition-Fed Preterm Pigs.

INTRODUCTION: Parenteral nutrition (PN) in preterm infants leads to PN-associated liver disease (PNALD). PNALD has been linked to serum accumulation of phytosterols that are abundant in plant oil but absent in fish oil emulsions. HYPOTHESIS: Whether modifying the phytosterol and vitamin E composition of soy and fish oil lipid emulsions affects development of PNALD in preterm pigs. METHODS: We measured markers of PNALD in preterm pigs that received 14 days of PN that included 1 of the following: (1) Intralipid (IL, 100% soybean oil), (2) Intralipid + vitamin E (ILE, d-α-tocopherol), (3) Omegaven (OV, 100% fish oil), or (4) Omegaven + phytosterols (PS, ß-sitosterol, campesterol, and stigmasterol). RESULTS: Serum levels of direct bilirubin, gamma glutamyl transferase, serum triglyceride, low-density lipoprotein, and hepatic triglyceride content were significantly lower (P < .05) in the ILE, OV, and PS compared to IL. Hepatic cholesterol 7-hydroxylase and organic solute transporter-α expression was lower (P < .05) and portal plasma FGF19 higher in the ILE, OV, and PS vs IL. Hepatic expression of mitochondrial carnitine palmitoyltransferase 1A and microsomal cytochrome P450 2E1 fatty acid oxidation genes was higher in ILE, OV, and PS vs IL. In vivo (13)C-CDCA clearance and expression of pregnane X receptor target genes, cytochrome P450 3A29 and multidrug resistance-associated protein 2, were higher in ILE, OV, and PS vs IL. CONCLUSIONS: α-tocopherol in Omegaven and added to Intralipid prevented serum and liver increases in biliary and lipidemic markers of PNALD in preterm piglets. The addition of phytosterols to Omegaven did not produce evidence of PNALD.

New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs.

Total parenteral nutrition (TPN) is associated with the development of parenteral nutrition-associated liver disease (PNALD) in infants. Fish oil-based lipid emulsions can reverse PNALD, yet it is unknown if they can prevent PNALD. We studied preterm pigs administered TPN for 14 days with either 100% soybean oil (IL), 100% fish oil (OV), or a mixture of soybean oil, medium chain triglycerides (MCTs), olive oil, and fish oil (SL); a group was fed formula enterally (ENT). In TPN-fed pigs, serum direct bilirubin, gamma glutamyl transferase (GGT), and plasma bile acids increased after the 14 day treatment but were highest in IL pigs. All TPN pigs had suppressed hepatic expression of farnesoid X receptor (FXR), cholesterol 7-hydroxylase (CYP7A1), and plasma 7α-hydroxy-4-cholesten-3-one (C4) concentrations, yet hepatic CYP7A1 protein abundance was increased only in the IL versus ENT group. Organic solute transporter alpha (OSTα) gene expression was the highest in the IL group and paralleled plasma bile acid levels. In cultured hepatocytes, bile acid-induced bile salt export pump (BSEP) expression was inhibited by phytosterol treatment. We show that TPN-fed pigs given soybean oil developed cholestasis and steatosis that was prevented with both OV and SL emulsions. Due to the presence of phytosterols in the SL emulsion, the differences in cholestasis and liver injury among lipid emulsion groups in vivo were weakly correlated with plasma and hepatic phytosterol content.