title: Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle.
abstract: Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation.
authors.affiliation: Department of Animal Sciences and Industry, Kansas State University, Manhattan, KS, USA.
authors.forename: Jaymelynn K
authors.initials: JK
authors.lastname: Farney
authors.forename: Laman K
authors.initials: LK
authors.lastname: Mamedova
authors.forename: Johann F
authors.initials: JF
authors.lastname: Coetzee
authors.forename: Butch
authors.initials: B
authors.lastname: KuKanich
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Sordillo
authors.forename: Sara K
authors.initials: SK
authors.lastname: Stoakes
authors.forename: J Ernest
authors.initials: JE
authors.lastname: Minton
authors.forename: Larry C
authors.initials: LC
authors.lastname: Hollis
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Bradford
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D007328:Insulin / Q000097:blood; D007774:Lactation / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012980:Sodium Salicylate / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D012980:Sodium Salicylate
keywords: homeorhesis; metabolism; salicylate