A Novel Adipocyte Population Arises From Bone Marrow Progenitor Cells

描述（由申请人提供）：三分之二的美国人超重或肥胖。身体脂肪过多，尤其是腹部脂肪过多，与心血管疾病、2型糖尿病、某些类型的癌症和其他疾病有关。预防体重增加或其对健康的有害影响的策略收效甚微。该项目将研究某些类型的脂肪细胞（脂肪细胞）是如何在腹部脂肪中产生的。该结果可能为预防体重增加和脂肪相关慢性疾病的治疗确定新的靶点。在过去的7年里，我们已经确定了一群由骨髓干细胞产生的脂肪细胞。这些干细胞离开骨髓，进入脂肪组织，在那里它们变成新的脂肪细胞。这些骨髓来源的脂肪细胞在雌性动物的腹部脂肪中优先积累，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。第一个目的是检测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

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.