title: Continuous low-dose infusion of tumor necrosis factor alpha in adipose tissue elevates adipose tissue interleukin 10 abundance and fails to alter metabolism in lactating dairy cows.
abstract: Repeated bolus doses of tumor necrosis factor-α (TNFα) alters systemic metabolism in lactating cows, but whether chronic release of inflammatory cytokines from adipose tissue has similar effects is unclear. Late-lactation Holstein cows (n=9-10/treatment) were used to evaluate the effects of continuous adipose tissue TNFα administration on glucose and fatty acid (FA) metabolism. Cows were blocked by feed intake and milk yield and randomly assigned within block to control or TNFα treatments. Treatments (4mL of saline or 14µg/kg of TNFα in 4mL of saline) were infused continuously over 7d via 2 osmotic pumps implanted in a subcutaneous adipose depot. Plasma, milk samples, milk yield, and feed intake data were collected daily, and plasma glucose turnover rate was measured on d 7. At the end of d 7, pumps were removed and liver and contralateral tail-head adipose biopsies were collected. Results were modeled with the fixed effect of treatment and the random effect of block. Treatment with TNFα increased plasma concentrations of the acute phase protein haptoglobin, but did not alter plasma TNFα, IL-4, IL-6, or IFN-γ concentrations, feed intake, or rectal temperature. Milk yield and composition were unchanged, and treatments did not alter the proportion of short- versus long-chain FA in milk on d 7. Treatments did not alter plasma free FA concentration, liver triglyceride content, or plasma glucose turnover rate. Surprisingly, TNFα infusion tended to decrease liver TNFα and IL-1 receptor 1 mRNA abundance and significantly increased adipose tissue IL-10 protein concentration. Continuous infusion of TNFα did not induce the metabolic responses previously observed following bolus doses delivered at the same rate per day. Metabolic homeostasis may have been protected by an adaptive anti-inflammatory response to control systemic inflammation.
authors.affiliation: Department of Animal Sciences and Industry, Kansas State university, Manhattan 66506.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Martel
authors.affiliation: Department of Animal Sciences and Industry, Kansas State university, Manhattan 66506.
authors.forename: Laman K
authors.initials: LK
authors.lastname: Mamedova
authors.affiliation: Department of Animal Sciences and Industry, Kansas State university, Manhattan 66506.
authors.forename: J Ernest
authors.initials: JE
authors.lastname: Minton
authors.affiliation: Veterinary Medical Teaching Hospital, Kansas State University, Manhattan 66506.
authors.forename: Meredyth L
authors.initials: ML
authors.lastname: Jones
authors.affiliation: Livestock Issues Research Unit, Agricultural Research Service, USDA, Lubbock, TX 79403.
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Carroll
authors.affiliation: Department of Animal Sciences and Industry, Kansas State university, Manhattan 66506. Electronic address: bbradfor@ksu.edu.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Bradford
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D005260:Female; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D055104:Infusions, Subcutaneous; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism*; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007774:Lactation; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008892:Milk / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000097:blood
chemical_list: D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D015850:Interleukin-6; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D005947:Glucose
keywords: adipose tissue; cytokine; inflammation; liver