Grant: Discovery Grants Program - Individual

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.