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.