title: Daily injection of tumor necrosis factor-{alpha} increases hepatic triglycerides and alters transcript abundance of metabolic genes in lactating dairy cattle.
abstract: To determine whether inflammation can induce bovine fatty liver, we administered recombinant bovine tumor necrosis factor-alpha (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 microg/(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-alpha (TNFalpha) and decreased feed intake. By d 7, feed intake of both rbTNF and pair-fed cows was approximately 15% less than CON (P < 0.01). Administration of rbTNF resulted in greater hepatic TNFalpha 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 TNFalpha promotes liver TG accumulation and suggest that inflammatory pathways may also be responsible for decreased glucose production in cows with fatty liver.
authors: Department of Animal Sciences and Industry, Kansas State University, Manhattan, KS 66506, USA. bbradfor@ksu.edu
authors: Barry J
authors: BJ
authors: Bradford
authors: Laman K
authors: LK
authors: Mamedova
authors: J Ernest
authors: JE
authors: Minton
authors: James S
authors: JS
authors: Drouillard
authors: Bradley J
authors: BJ
authors: Johnson
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002417:Cattle; D002418:Cattle Diseases / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000662:veterinary*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000662:veterinary*; D007279:Injections, Subcutaneous; D007774:Lactation / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D011995:Recombination, Genetic; D014280:Triglycerides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C053809:1-acylglycerophosphoethanolamine acyltransferase; D000217:Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D005952:Glucose-6-Phosphatase