Influence of menopause on adipose tissue accumulation and function

项目摘要 绝经与雌二醇（E2）的下降有关，雌二醇（E2）的下降与雌二醇（E2）的显著积累相一致。 腹部脂肪组织（AT）。然而，很少有人知道雌二醇的损失是否会改变仓库特异性AT 以促进腹部肥胖的方式扩张和发挥功能。目前尚不清楚是否增加 伴随绝经的腹部AT肿块是由于脂肪生成增加或其他机制， 如肥大增加或脂质储存改变。我们对绝经前与雌激素缺乏的研究， 绝经后妇女将使我们能够检查雌激素戒断作为脂肪形成的机制（目的1） 以及在皮下腹部和股部储库内的AT功能改变（Aim 2）， 探讨了我们的总体假设是，绝经期E2的损失促进腹部脂肪的形成 并损害AT功能。我们将是第一个确定雌激素中潜在的新的储存库特异性AT途径的人。 耗尽，绝经后妇女解释在腹部肥胖的积累，发生与 绝经从我们的研究中获得的知识将使我们能够设计和实施更有针对性的 预防女性腹部AT蓄积的干预方法。获得的技能和职业 在这个K01提案的发展计划将使我成为一个独立的，NIH资助的科学家， 女性健康研究，整合治疗，以减少腹部肥胖和改善代谢健康 中年女性的

PROJECT SUMMARY Menopause is associated with a decline in estradiol (E2) that coincides with a significant accumulation of abdominal adipose tissue (AT). Yet, little is known about whether the loss of estradiol alters depot-specific AT expansion and function in a manner that promotes abdominal adiposity. It is unknown whether the increased abdominal AT mass that accompanies menopause is due to increased adipogenesis or other mechanisms such as increased hypertrophy or altered lipid storage. Our studies of premenopausal versus estrogen-depleted, postmenopausal women will allow us to examine estrogen withdrawal as a mechanism for adipogenesis (Aim 1) and altered AT function (Aim 2) within the subcutaneous abdominal and femoral depots that has not been explored. Our overarching hypothesis is that E2 loss with menopause promotes abdominal adipogenesis and impair AT function. We would be the first to identify potential novel depot-specific AT pathways in estrogen- depleted, postmenopausal women to explain the accumulation in abdominal adiposity that occurs with menopause. Knowledge gained from our studies will allow us to design and implement more targeted approaches for intervention that prevent abdominal AT accumulation in women. The acquired skills and career development plan in this K01 proposal will allow me to emerge as an independent, NIH-funded scientist in women’s health research that integrates treatments to reduce abdominal adiposity and improve metabolic health in midlife women.