Metabolic Responses to Prolonged Fasting in a Naturally Obese Marine Mammal

William Knox Holt Memorial Library and Learning Center

Many animals undergo fasting in order to survive during periods of severe weather, food scarcity, migration, or reproduction. While most animals decrease their metabolism while fasting, northern elephant seals fast for several months while undergoing energy-intensive activities such as molting and reproduction. Seals fuel their energy needs with large fat stores that they accumulate while foraging at sea, resembling human patients with diabetes and obesity (insulin sensitivity, high levels of glucose and fat) while fasting. While some of the hormone signals involved in fasting have been identified, the molecular mechanisms that regulate healthy metabolic adaptations to fasting in seals are not fully understood. We used proteome sequencing to examine changes in protein abundance in blood plasma and the main energy-utilizing (skeletal muscle) and energy-storing (blubber) tissues of adult female elephant seals over their five-week molting fast. We found that while blubber and muscle proteomes were remarkably stable over fasting, over 50 proteins changed in abundance in plasma, including those associated with fat storage, metabolism, and transport. Apolipoproteins, which are key components of cholesterol and fat-transporting particles (such as HDL and LDL), dominated proteome responses to fasting. Apolipoproteins associated with fat storage decreased, while those associated with fat burning and HDL function increased over fasting. Our findings suggest that changes in apolipoprotein composition may mediate the metabolic transitions between feeding and fasting and underlie metabolic health in elephant seals. Many of these proteins have not been previously studied in this species and provide intriguing hypotheses about metabolic regulation during prolonged fasting in mammals.