TY - JOUR
T1 - Daily injection of tumor necrosis factor-α increases hepatic triglycerides and alters transcript abundance of metabolic genes in lactating dairy cattle
AU - Bradford, Barry J.
AU - Mamedova, Laman K.
AU - Minton, J. Ernest
AU - Drouillard, James S.
AU - Johnson, Bradley J.
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=67749119780&partnerID=8YFLogxK
U2 - 10.3945/jn.109.108233
DO - 10.3945/jn.109.108233
M3 - Article
C2 - 19549751
AN - SCOPUS:67749119780
SN - 0022-3166
VL - 139
SP - 1451
EP - 1456
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 8
ER -