Date of Graduation
Davis College of Agriculture, Natural Resources and Design
Agricultural and Resource Economics
Joseph W McFadden
Scott A Bowdridge
K Marie Krause
Joseph W McFadden
Dairy cows transitioning from gestation to lactation experience insulin resistance as maternal adaptation to partition nutrients toward the mammary gland to support milk production. Insulin resistance causes increased lipolysis and free fatty acid (FFA) release into circulation. Unfortunately, this metabolic adaptation occurs during a time when energy demands are heightened and cows are already experiencing negative energy balance. As a result, accelerated hepatic FFA influx promotes hepatic triacylglycerol (TAG) accumulation and ketogenesis, which can cause postpartum metabolic disease. In diabetic monogastrics, mechanisms that mediate insulin resistance involve the sphingolipid ceramide. The role of ceramide in insulin signaling in dairy cows transitioning from gestation to lactation has not been previously established. The studies presented in this master of science thesis evaluate the relationship between fatty acid availability, ceramide synthesis, and insulin sensitivity. In the first experiment, we tested the hypothesis that ceramide accumulates in dairy cows experiencing lipolysis and insulin resistance. We show that nutrient restriction (NR) increased serum fatty acids and ceramide levels, and impaired insulin sensitivity; however, infusion with nicotinic acid (NA), a known suppressor of lipolysis, was unable to prevent these responses. We also showed that NR increased hepatic ceramide accumulation, a response that was positively associated with serum ceramide supply. Our data demonstrate that circulating and hepatic 24:0-Cer are inversely associated with systemic insulin tolerance, an effect not observed for the 16:0 moiety. In the second experiment, our objective was to characterize relationship between prepartum adiposity and insulin sensitivity in dairy cows transitioning from gestation to lactation. Our data demonstrate that during the periparturient period, FFA, BHBA, and liver lipid increase, more so for overweight cows. While plasma glucose and serum insulin were not affected by adiposity, serum insulin concentrations decreased postpartum. Using a hyperinsulinemic-euglycemic clamp (HEC) technique to directly measure insulin sensitivity, we show that steady state serum glucose, insulin, and FFA levels were not modified by adiposity. HEC glucose infusion rate was not affected by adiposity, but systemic insulin resistance developed in overweight cows postpartum when accounting for changes in insulin and glucose. Insulin-stimulated phosphorylation of subcutaneous adipose tissue AKT was not modified by adiposity, but AKT phosphorylation significantly decreased from pre- to postpartum. Collectively, these data demonstrate that adiposity does not affect adipose tissue-specific insulin signaling, even though it did impair insulin sensitivity as indicated by the SIClamp.
Davis, Amanda Nicole, "Characterizing the Mechanisms of Insulin Resistance in Dairy Cattle" (2017). Graduate Theses, Dissertations, and Problem Reports. 7075.