Genetic investigations into adiponectin as a biologic mediator and a therapeutic

非洲裔美国人较高的胰岛素抵抗被认为是不成比例的易感因素。 人们对包括肥胖症、2型糖尿病和心血管疾病在内的一系列心脏代谢疾病的风险也很高。 我们试图将这一流行病学发现转化为一种假设，即胰岛素与胰岛素之间的反向关系 耐药性和脂肪细胞特异性激素脂联素可以作为新的治疗方案的基础。 心脏代谢紊乱。大量文献证实了胰岛素增敏、抗炎和 脂联素的心脏保护作用。也有大量证据表明脂联素存在种族差异。 级别。更具体地说，非裔美国人的脂联素水平较低，这在一定程度上可以解释较高的水平。 这一人群中的胰岛素抵抗和伴随的心脏代谢疾病风险。基因的多态现象 脂联素基因与高加索人和亚洲人的脂联素水平和胰岛素敏感性相关 然而，在非洲，脂联素的可比性多态图谱严重缺乏。 美国人。此外，尽管积累了对脂联素功能的某些机械见解，但完整的 脂联素的生物学谱还没有通过系统生物学的方法来阐明。最后，适用于 评价从遗传和系统生物学中鉴定的候选脂联素调节剂的体外试验 方法也是缺乏的。为了解决这些差距，我们建议在细胞、动物 和人群水平，以批判性地评价脂联素作为生物介体和可能的治疗靶点 用于降低心脏代谢风险。拟议研究背后的统一目标是扩大我们的 了解脂联素生物学，参考健康差距和开发关键资源 使未来对脂联素修饰治疗的研究成为可能。因为低脂联素血症经常 在非洲裔美国人中观察到，我们的研究对解决以下问题具有额外的意义 少数族裔人口。

Higher insulin resistance in African Americans has been suggested to disproportionately predispose this population to a host of cardio-metabolic disorders including obesity, type 2 diabetes and cardiovascular disease. We seek to transform this epidemiologic finding into the hypothesis that the inverse relationship between insulin resistance and the adipocyte-specific hormone, adiponectin, can be the basis for a novel treatment paradigm in cardio-metabolic disorders. A significant body of literature confirms the insulin-sensitizing, anti-inflammatory and cardioprotective properties of adiponectin. There is also substantial evidence of ethnic variation in adiponectin levels. More specifically, adiponectin levels are lower in African Americans and could partly explain the higher insulin resistance and attendant cardio-metabolic disease risk in this population. Polymorphisms in the adiponectin gene have been associated with adiponectin levels and insulin-sensitivity in Caucasian and Asian populations; however, there is a critical lack of comparable polymorphism mapping of adiponectin in African Americans. Also, despite the accumulation of certain mechanistic insights into adiponectin function, the full spectrum of adiponectin biology is yet to be elucidated through systems biology approaches. Finally, suitable in vitro assays for evaluating candidate adiponectin regulators identified from genetic and systems biology approaches are also lacking. To address these gaps, we propose translational research at the cellular, animal and population levels to critically evaluate adiponectin as a biologic mediator of, and a possible therapeutic target for, cardio-metabolic risk reduction. The unifying objective behind the proposed study is expansion of our understanding of adiponectin biology with reference to health disparities and development of key resources for enabling future investigations into adiponectin-modifying treatments. Since hypoadiponectinemia is frequently observed in African-Americans, our research carries added significance for addressing health disparities in minority populations.