Influence of menopause on adipose tissue accumulation and function

项目总结 更年期与雌二醇(E_2)的下降有关，而雌二醇(E_2)的下降与体内 腹部脂肪组织(AT)。然而，关于雌激素的丧失是否会改变仓库特有的AT，人们知之甚少 以一种促进腹部肥胖的方式扩张和功能。目前尚不清楚是否增加了 伴随绝经的腹部AT肿块是由于脂肪生成增加或其他机制 如肥厚增加或脂肪储存改变。我们对绝经前和雌激素耗竭的研究， 绝经后妇女将允许我们检查雌激素停用作为脂肪形成的机制(目标1)。 和改变的AT功能(目标2)在皮下腹部和股动脉库内，尚未 探索过了。我们的主要假设是绝经后雌激素的丢失会促进腹部脂肪生成。 并损害AT功能。我们将是第一个发现雌激素中潜在的特定于仓库的AT通路的人- 绝经后精疲力竭的妇女解释腹型肥胖症的累积 更年期。从我们的学习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积聚的干预方法。获得的技能和职业 这份K01提案中的发展计划将使我成为一名独立的、由NIH资助的科学家 综合治疗以减少腹部肥胖和改善代谢健康的女性健康研究 在中年女性中。

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.