Daily injection of tumor necrosis factor-α increases hepatic triglycerides and alters transcript abundance of metabolic genes in lactating dairy cattle

Barry J. Bradford, Laman K. Mamedova, J. Ernest Minton, James S. Drouillard, Bradley J. Johnson

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

To determine whether inflammation can induce bovine fatty liver, we administered recombinant bovine tumor necrosis factor-a (rbTNF) to late-lactation Holstein cows. Cows (n = 5/treatment) were blocked by feed intake and parity and randomly assigned within block to control (CON; saline), rbTNF at 2 μg/(kg·d), or pair-fed control (saline, intake matched) treatments. Treatments were administered once daily by subcutaneous injection for 7 d. Plasma samples were collected daily for analysis of glucose and FFA and a liver biopsy was collected on d 7 for triglyceride (TG) and quantitative RT-PCR analyses. Data were analyzed using treatment contrasts to assess effects of tumor necrosis factor-α (TNFα) and decreased feed intake. By d 7, feed intake of both rbTNF and pair-fed cows was ∼15% less than CON (P < 0.01). Administration of rbTNF resulted in greater hepatic TNFα mRNA and protein abundance and 103% higher liver TG content (P < 0.05) without affecting the plasma FFA concentration. Hepatic carnitine palmitoyltransferase 1 transcript abundance tended to be lower (P = 0.09) and transcript abundance of fatty acid translocase and 1-acyl-glycerol-3-phosphate acyltransferase was higher (both P < 0.05) after rbTNF treatment, consistent with increased FFA uptake and storage as TG. Transcript abundance of glucose-6-phosphatase (P < 0.05) and phosphoenolpyruvate carboxykinase 1 (P = 0.09), genes important for gluconeogenesis, was lower for rbTNF-treated cows. These findings indicate that TNFα promotes liver TG accumulation and suggest that inflammatory pathways may also be responsible for decreased glucose production in cows with fatty liver.

Original languageEnglish
Pages (from-to)1451-1456
Number of pages6
JournalJournal of Nutrition
Volume139
Issue number8
DOIs
StatePublished - Aug 2009

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