Body condition, n-3/n-6 PUFA balance and the regulation of lipid and glucose metabolism in the mink

水貂护理病是一种以血糖调节受损为特征的代谢紊乱。当哺乳期的需求需要广泛调动身体能量储备时，就会发生这种情况。过胖或过瘦的女性表现出更高的血糖水平变异性，并损害了健康和生殖。众所周知，体内脂肪储备的快速动员会导致脂肪肝(肝脏脂肪沉积症)、omega-3多不饱和脂肪酸(n-3 PUFA)的丢失和胰岛素抵抗的发展。这项研究计划的长期目标是了解脂肪肝综合征的潜在生物学及其与水貂护理疾病的关系。我计划研究身体状况、脂肪酸营养和管理实践之间的关系，如饲养强度和快速减肥，以及对水貂体内脂肪和血糖代谢的调节。我的目的是研究营养状况对代谢反应和参与体内脂肪和血糖代谢的关键酶的基因表达的影响。将进行饲养实验，在两种饲养强度水平下饲养的水貂将引入不同的脂肪酸谱，以诱导瘦肉和肥胖的身体状况。针对短期禁食，我们将研究快速减肥的效果。我还将评估具有不同n-3/n-6多不饱和脂肪酸图谱的水貂的氧化应激水平和炎症标志物。此外，我想研究禁食诱导的肝脂沉积过程中肝组织中未折叠蛋白质包涵体(Mallory小体)的形成，并利用培养的肝细胞更密切地研究它们在脂肪肝疾病中的作用。

Mink nursing sickness is a metabolic disorder characterized by impaired blood sugar regulation. It occurs when the demands for lactation require extensive mobilization of body energy reserves. Females that are either too heavy or too thin show higher variability in their blood sugar levels and have impaired health and reproduction. Rapid mobilization of body fat reserves is known to result in fatty liver (hepatic lipidosis), loss of the omega-3 polyunsaturated fatty acids (n-3 PUFA) and the development of insulin resistance. The long term goals of this research program are to understand the underlying biology of fatty liver syndrome and its association with mink nursing sickness. I plan to investigate the relationships that exist between body condition, fatty acid nutrition and management practices, such as feeding intensity and rapid weight loss, and the regulation of body fat and blood sugar metabolism in the mink. My objectives are to study the impact of the nutritional status on the metabolic response and the gene expression of key enzymes participating in body fat and blood sugar metabolism. Feeding experiments will be carried out where varying fatty acid profiles will be introduced to mink fed at two feeding intensity levels to induce lean and obese body conditions. The effects of rapid weight loss will be examined in response to short term fasting. I will also evaluate the level of oxidative stress and markers of inflammation in the mink with different n-3/n-6 PUFA profiles. In addition, I want to examine the formation of unfolded protein inclusions (Mallory bodies) in the liver tissue during fasting-induced hepatic lipidosis and more closely investigate their role in the fatty liver disease using cultured hepatocytes.