Crocker Daniel E, Fowler Melinda A, Champagne Cory D, Vanderlugt Anna L, Houser Dorian S
Sonoma State University, Rohnert Park, CA 94928, USA.
Sonoma State University, Rohnert Park, CA 94928, USA; Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
Gen Comp Endocrinol. 2014 Jan 1;195:99-106. doi: 10.1016/j.ygcen.2013.11.005. Epub 2013 Nov 13.
Metabolic adaptations for extended fasting in wildlife prioritize beta-oxidation of lipids and reduced glucose utilization to support energy metabolism. The pancreatic hormone glucagon plays key roles in regulating glycemia and lipid metabolism during fasting in model species but its function in wildlife species adapted for extended fasting is not well understood. Northern elephant seals (NES) undergo natural fasts of 1-3months while under constraints of high nutrient demands including lactation and development. We performed a glucagon challenge on lactating, molting and developing NES, early and late in their natural fasts, to examine the impact of this important regulatory hormone on metabolism. Glucagon caused increases in plasma glucose, insulin, fatty acids, ketones and urea, but the magnitude of these effects varied widely with adiposity and life-history stage. The strong impact of adiposity on glucose and insulin responses suggest a potential role for adipose derived factors in regulating hepatic metabolism and pancreatic sensitivity. Elevations in plasma glucose in response to glucagon were strongly associated with increases in protein catabolism, suggesting negative impacts of elevated glucagon on protein sparing. Glucagon promoted rapid ketone accumulation suggesting that low ketoacid levels in NES reflect low rates of production. These results demonstrate strong metabolic impacts of glucagon and support the idea that glucagon levels are downregulated in the context of metabolic adaptation to extended fasting. These results suggest that the regulation of carbohydrate and lipid metabolism in NES changes with adiposity, fasting duration and under various constraints of nutrient demands.
野生动物长时间禁食的代谢适应优先考虑脂质的β-氧化和降低葡萄糖利用，以支持能量代谢。胰腺激素胰高血糖素在模式物种禁食期间调节血糖和脂质代谢中起关键作用，但其在适应长时间禁食的野生动物物种中的功能尚不清楚。北象海豹在包括哺乳和发育在内的高营养需求限制下会经历1至3个月的自然禁食。我们在自然禁食的早期和晚期，对正在哺乳、蜕皮和发育的北象海豹进行了胰高血糖素激发试验，以研究这种重要调节激素对代谢的影响。胰高血糖素导致血浆葡萄糖、胰岛素、脂肪酸、酮和尿素增加，但这些影响的程度因肥胖程度和生活史阶段而有很大差异。肥胖对葡萄糖和胰岛素反应的强烈影响表明脂肪衍生因子在调节肝脏代谢和胰腺敏感性方面可能发挥作用。对胰高血糖素反应时血浆葡萄糖的升高与蛋白质分解代谢的增加密切相关，表明胰高血糖素升高对蛋白质节约有负面影响。胰高血糖素促进了酮的快速积累，这表明北象海豹中低酮酸水平反映了低生成率。这些结果证明了胰高血糖素对代谢有强烈影响，并支持在对长时间禁食的代谢适应背景下胰高血糖素水平下调的观点。这些结果表明，北象海豹中碳水化合物和脂质代谢的调节随肥胖程度、禁食持续时间以及在各种营养需求限制下而变化。
