Dietary Protein Restriction Remodels Adipose Tissue to Defend Against Age-Related Metabolic Decline

摘要 脂肪组织是代谢健康的关键内分泌介质，其在衰老过程中功能改变， 肥胖我们的数据表明，膳食蛋白质限制（DPR）增加全身葡萄糖 体内平衡和能量消耗，并防止与年龄相关的代谢下降，这些 代谢效应与白色脂肪组织的重塑有关， 标志物和脂联素分泌。这个项目测试的假设，脂肪组织的重塑 在饮食中限制蛋白质直接改善衰老过程中的代谢健康。该模型将由 评估脂肪组织中促进葡萄糖生成的转录和细胞信号传导途径 体内平衡和胰岛素敏感性，并确定这些中的哪些在一个年龄段的DPR期间改变- 依赖的方式。最后，我们将测试脂联素的增加是否有助于全身 蛋白质限制期间葡萄糖稳态的改善，以及是否使用来自 蛋白质限制的小鼠以脂联素依赖的方式对抗年龄相关的胰岛素抗性。

Abstract Adipose tissue is a critical endocrine mediator of metabolic health that is functionally altered during aging and obesity. Our data demonstrate that dietary protein restriction (DPR) increases whole body glucose homeostasis and energy expenditure and protects against age-related metabolic decline, and that these metabolic effects are associated with a remodeling of white adipose tissue that includes increased thermogenic markers and adiponectin secretion. This project tests the hypothesis that the remodeling of adipose tissue during dietary protein restriction directly improves metabolic health during aging. This model will be tested by assessing the transcriptional and cell signaling pathways in adipose tissue that contribute to glucose homeostasis and insulin sensitivity and determining which of these are altered during DPR in an age- dependent fashion. Lastly, we will test whether increases in adiponectin contribute to whole body improvements in glucose homeostasis during protein restriction, and whether using adipose tissue grafts from protein restricted mice combats age-related insulin resistance in an adiponectin-dependent manner.