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，在衰老和 肥胖。我们的数据表明，限制饮食蛋白质(DPR)会增加全身葡萄糖 动态平衡和能量消耗，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，包括产热增加 标志物和脂联素的分泌。这个项目测试了脂肪组织重塑的假说 在饮食期间，限制蛋白质直接改善衰老期间的新陈代谢健康。该型号将由以下人员进行测试 评估脂肪组织中与葡萄糖有关的转录和细胞信号通路 动态平衡和胰岛素敏感性，并确定其中哪些会在某个年龄的DPR期间发生变化- 依附时尚。最后，我们将测试脂联素的增加是否对全身有贡献 限制蛋白质期间葡萄糖稳态的改善，以及是否使用脂肪组织移植 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抵抗。

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.