title: Effects of the insulin sensitizing drug, pioglitazone, and lipopolysaccharide administration on markers of systemic inflammation and clinical parameters in horses.
abstract: Equine metabolic syndrome (EMS) is a condition of obese horses characterized by insulin resistance, systemic inflammation, and an increased risk of laminitis. The pathogenesis of EMS is thought, in part, to be due to inflammatory proteins produced by adipose tissue. Reducing inflammation may decrease the incidence of laminitis in horses with EMS. Pioglitazone hydrochloride, a thiazolidinedione, has efficacy to reduce obesity associated inflammation in humans. Eight normal, adult, horses were administered 1mg/kg pioglitazone for 14 days, and eight horses served as controls. Physical examination and hematologic variables, transcript abundance of pro-inflammatory cytokines in skeletal muscle and adipose tissue, and circulating concentrations of the acute phase protein, serum amyloid A and pro-inflammatory cytokine, TNF-α were assessed prior to, and following, an LPS infusion (35 ng/kg). The objective was to determine if pre-treatment with pioglitazone would mitigate the development of inflammation and associated clinical markers of inflammation following LPS administration. Lipopolysaccharide administration induced systemic inflammation, as assessed by clinical and hematological aberrations, increased TNF-α, SAA and adipose tissue IL-6 mRNA abundance, however no mitigating effects of pioglitazone were detected. A longer treatment period or higher dose might be indicated for future experiments.
authors.affiliation: Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060-0443, USA.
authors.forename: Jamie G
authors.initials: JG
authors.lastname: Wearn
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Suagee
authors.forename: Mark V
authors.initials: MV
authors.lastname: Crisman
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Corl
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Hulver
authors.forename: David R
authors.initials: DR
authors.lastname: Hodgson
authors.forename: Ray J
authors.initials: RJ
authors.lastname: Geor
authors.forename: Laura J
authors.initials: LJ
authors.lastname: McCutcheon
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry / Q000187:drug effects; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D018932:Chemokine CCL2 / Q000032:analysis; D054412:Chemokine CCL8 / Q000032:analysis; D005260:Female; D006734:Horse Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006736:Horses / Q000097:blood / Q000276:immunology; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*; D053583:Interleukin-1beta / Q000032:analysis / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D016209:Interleukin-8 / Q000032:analysis; D020738:Leptin / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects; D000077205:Pioglitazone; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D054412:Chemokine CCL8; D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D020738:Leptin; D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077205:Pioglitazone