Obesity and Hematopoiesis

肥胖与造血

• 批准号: 9086341
• 负责人: DANICA CHEN
• 金额: $ 31.4万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9086341
• 关键词: Adverse effects; Affect; Allogeneic Bone Marrow Transplantation; Animals; Apoptosis; Autologous; Biochemical; Biochemical Pathway; Biological; Cell Maintenance; Cell Proliferation; Cell physiology; Cells; Cellular Metabolic Process; Chromatin; Decision Making; Defect; Diet; Foundations; Health; Hematologic Neoplasms; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Homeostasis; Human; Immune; Individual; Lead; Link; Mediating; Metabolic; Metabolism; Mitochondria; Modeling; Molecular; Nutrient; Nutritional; Obese Mice; Obesity; Pathway interactions; Patients; Physiological; Play; Process; Regulation; Research; Resistance; Risk; Role; Social Impacts; Solid; Stress; System; Testing; base; immune function; mortality; mouse model; nuclear respiratory factor; programs; self-renewal; sensor; stemness; tissue/cell culture

Summary Obesity perturbs metabolic homeostasis and has adverse effects on health. Obese patients have compromised immune function, increased risk for a hematological malignancy, and increased risk for non-relapse mortality following either autologous or allogeneic bone marrow transplantation. Abnormalities in hematopoiesis occur in obese individuals and may underlie their compromised immune and hematopoietic functions. We propose to investigate the molecular and cellular mechanisms that underlie deregulated hematopoiesis in obese patients. The overall hypothesis to be investigated is that obesity perturbs metabolic homeostasis in hematopoietic stem cells (HSCs), resulting in compromised HSC function and hematopoiesis. Supporting this hypothesis is our recent finding that a nutrient sensor, whose activity is inversely regulated by nutritional input, regulates mitochondrial metabolic homeostasis to promote stress resistance in HSCs and promotes their self-renewal and hematopoiesis under stress. We plan to greatly expand this initial finding to systemically investigate how obesity affects HSC function and hematopoiesis.

摘要 肥胖会扰乱新陈代谢平衡，并对健康产生不利影响。肥胖 患者免疫功能受损，血液疾病风险增加 恶性肿瘤，以及自体或自体移植后非复发死亡风险增加 异基因骨髓移植。肥胖者会出现造血功能异常 这可能是他们免疫和造血功能受损的原因。 我们建议研究分子和细胞机制。 肥胖患者的非调节性造血功能。要研究的总体假设 肥胖扰乱了造血干细胞(HSCs)的代谢动态平衡， 导致肝星状细胞功能和造血功能受损。支持这一假设的是 我们最近发现，一种营养传感器，其活动受 营养输入，调节线粒体代谢动态平衡，促进应激 HSCs在应激状态下的抗性，并促进其自我更新和造血。 我们计划极大地扩展这一初步发现，以系统地研究肥胖是如何 影响HSC功能和造血功能。