Sphingolipid Metabolism and Insulin Resistance in Dairy Cattle

• Main Author: Navarrete, Jorge Eduardo Rico
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01.01.2016
• Subjects: Animal sciences; Biochemistry; Nutrition
• ISBN: 1339734672; 9781339734675

During their productive and reproductive life cycles, dairy cows naturally undergo physiological adaptations that facilitate modifications of nutrient flux to sustain the energy demands of gestation and lactation. The onset of lipolysis from adipose tissue is necessary to sustain tissue energy supply while cows experience sustained negative energy balance during early lactation. Excessive lipomobilization, however, predisposes dairy cows to metabolic disease during postpartum, leading to poor health, reduced productive and reproductive performance, increased rates of culling, and economic losses for the industry. In monogastrics, ceramides are implicated in the pathogenesis of insulin resistance, and are associated with saturated fatty acid availability and the onset of metabolic diseases. To date, the role of ceramides and its association with insulin action during peripartum and established lactation, have not been investigated in dairy cows. The studies presented in this dissertation evaluate the associations between fatty acid availability, ceramide synthesis, and insulin action. In the first and second experiment, we established that increased body fat accumulation results in elevated circulating NEFA, ketone bodies and liver fat accumulation, reduced plasma sphingomyelin, and increased ceramide content in plasma, liver and skeletal muscle. Ceramides were inversely associated with circulating insulin and insulin sensitivity. Time-specific effects were observed for insulin ceramide accumulation, which increased during the transition from gestation to lactation, and were independent of adiposity. Similarly, plasma sphingomyelins, a source of ceramides, decreased toward parturition and increased postpartum. Ceramide accumulation in plasma was associated with hepatic fat accumulation and hepatic ceramide availability. In the third experiment, the effects of feeding palmitate (C16:0; 4% of ration DM) were characterized in dairy cows during mid-lactation. Palmitate supplementation resulted in increased hepatic accumulation of ceramides and modulation of genes related to ceramide synthesis. Similarly, palmitate supplementation increased circulating ceramide concentration, a response both positively associated with milk yield and negatively associated with circulating NEFA disappearance during an intravenous glucose challenge. Interestingly, palmitate supplementation delayed time-associated decrease of circulating ceramide during lactation. Collectively, these results demonstrate that availability of circulating fatty acids can impact ceramide synthesis and suggest that insulin action is associated with ceramide accumulation. Moreover, time-dependent changes occur in sphingolipid availability during the cow life cycle, indicating a possible role of ceramides in the physiological adaptations that allow preservation of energy homeostasis. These studies provide a framework for the study peripartal and lactational insulin resistance in association with sphingolipid metabolism.