A Novel Adipocyte Population Arises From Bone Marrow Progenitor Cells

骨髓祖细胞产生新的脂肪细胞群

• 批准号: 9064766
• 负责人: Dwight J Klemm
• 金额: $ 33.82万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9064766
• 关键词: Abdomen; Accounting; Address; Adipocytes; Adipose tissue; Adult; American; Animals; Biogenesis; Body fat; Bone Marrow; Bone Marrow Stem Cell; Cardiovascular Diseases; Cells; Characteristics; Chronic Disease; Comorbidity; Data; Developed Countries; Development; Disease; Estrogens; Exhibits; Fatty acid glycerol esters; Female; Gender; Gene Expression Profile; Generations; Genetic; Goals; Gonadal Steroid Hormones; Health; Heterogeneity; High Fat Diet; Hormones; Inflammatory; Knockout Mice; Label; Laboratories; Leptin; Link; Lipids; Location; Macrophage Inflammatory Proteins; Malignant Neoplasms; Marrow; Measurement; Measures; Medical; Menopause; Mitochondria; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Ovarian hormone; Overweight; Phenotype; Play; Population; Process; Production; Progesterone; Proteins; Reporting; Research; Risk; Role; Stem cells; Techniques; Testing; Thiazolidinediones; Time; Tissues; Travel; Visceral; Weight Gain; Woman; abdominal fat; bone; cytokine; design; effective therapy; feeding; improved; male; men; monocyte; new therapeutic target; novel; oxidation; prevent; progenitor; research study; statistics; subcutaneous; success

DESCRIPTION (provided by applicant): Two thirds of Americans are overweight or obese. Excess body fat, particularly in the abdomen, has been linked to cardiovascular disease, type 2 diabetes, certain forms of cancer and other medical conditions. Strategies to prevent weight gain or its harmul effects on health have had limited success. This project will investigate how certain types of fat-toring cells (adipocytes) are produced in abdominal fat. The results may identify new targets for therapie to prevent weight gain and fat-related chronic disease. Over the last 7 years we have identified a population of adipocytes that are produced from stem cells in the bone marrow. These stem cells leae the marrow and travel to fat tissue where they become new adipocytes. These bone marrow-derived adipocytes accumulate preferentially in abdominal fat in female animals, and exhibit potentially hamful characteristics. This project is designed to determine why these cells are produced in abdominal fa, and if their production is more rapid than other types of fat-storing cells. The first aim will tes whether the inflammatory protein, monocyte inhibitory protein-1a (MIP-1a), promotes the recruitment of stem cells from the bone marrow to fat and the subsequent generation of bone marrow-derived adipocyte in abdominal fat. This will be accomplished by following labeled marrow progenitors to fat tissue in mce in which MIP-1a has been genetically erased. Aim 2 will test whether the ovarian hormones, estrogen an progesterone, are also involved in bone marrowadipocyte production and account for the preferential accumulation of these fat cells in female subjects. Finally, Aim 3 will use a novel labeling technoogy to measure the rate at which bone marrow-derived adipocytes and other fat-storing cells are produced i fat in different body locations. Completion of these studies will provide a comprehensive picture o the factors and processes that control bone marrow-derived adipocyte production. The results are likelyto highlight new targets for controlling the generation of these fat cells and thereby mitigate their armful effects on health. The results may also ex- plain why fat is stored differently between men and womn, and why fat storage in women changes after menopause. We predict that these experiments will furthe underscore the importance of stem cells and progenitor cells in the development of fat in differentbody locations and its differential impact on health.

描述（由申请人提供）：三分之二的美国人超重或肥胖。体内过多的脂肪，尤其是腹部的脂肪，与心血管疾病、2型糖尿病、某些癌症和其他疾病有关。防止体重增加或其对健康造成有害影响的策略取得的成功有限。该项目将研究腹部脂肪中如何产生某些类型的脂肪细胞（脂肪细胞）。研究结果可能会确定预防体重增加和与脂肪相关的慢性疾病的新治疗目标。在过去的 7 年里，我们已经鉴定出由骨髓中的干细胞产生的脂肪细胞群。这些干细胞离开骨髓并前往脂肪组织，在那里它们成为新的脂肪细胞。这些骨髓来源的脂肪细胞优先积聚在雌性动物的腹部脂肪中，并表现出潜在的有害特征。该项目旨在确定为什么这些细胞在腹部脂肪中产生，以及它们的产生是否比其他类型的脂肪储存细胞更快。第一个目标将测试炎症蛋白、单核细胞抑制蛋白-1a (MIP-1a) 是否促进干细胞的募集。 细胞从骨髓到脂肪以及随后产生的骨髓来源的脂肪细胞 腹部脂肪。这将通过跟踪标记的骨髓祖细胞到 mce 中的脂肪组织来实现，其中 MIP-1a 已被基因擦除。目标 2 将测试卵巢激素（雌激素和黄体酮）是否也参与骨髓脂肪细胞的产生并解释优先性 这些脂肪细胞在女性受试者中积累。最后，Aim 3 将使用一种新颖的标记技术来测量骨髓来源的脂肪细胞和其他脂肪储存细胞在不同身体部位的脂肪中产生的速率。这些研究的完成将全面了解控制骨髓来源脂肪细胞产生的因素和过程。研究结果可能会突出控制这些脂肪细胞生成的新目标，从而减轻它们对健康的严重影响。研究结果还可以解释为什么男性和女性的脂肪储存量不同，以及为什么女性的脂肪储存量在绝经后发生变化。我们预测这些实验将进一步强调干细胞和祖细胞在身体不同部位脂肪形成中的重要性及其对健康的不同影响。