白脂素通过cAMP-PKA-CREB通路调控前体脂肪细胞成脂分化及其在多囊卵巢综合征脂代谢中的作用研究

Aberrant lipid metabolism is one of the most common features in patients with PCOS, but the etiology is still unclear. Asprosin is newly discovered fasting-induced glucogenic protein hormone which is the C-terminal cleavage production of profibrillin1.Our previous study showed that adipose tissue from patients with PCOS expressed higher levels of FBN1, meanwhile higher levels of asprosin in the serum. What is more, the levels of asprosin were positively associated with testosterone. Our research group purified the recombinant protein asprosin and found that it could promote the differentiation of pre-adipocyte and adipose mesenchymal stem cell and active the cAMP-PKA-CREB pathway. Therefore, our hypothesis is that hyperandrogen promoted asprosin expression and asprosin induced the differentiation of pre-adipocyte and adipose mesenchymal stem cell to promote lipid biosynthesis and lipid droplet formation through cAMP-PKA-CREB pathway. Our research will explore the mechanism of how asprosin contributed to the aberrant lipid metabolism in PCOS disease through in vitro and in vivo study, which will provide novel evidence for treatment.

脂代谢异常是多囊卵巢综合征（PCOS）最常见的远期并发症，其具体机制尚未阐明。白脂素（asprosin）是最新发现由脂肪组织分泌的升血糖蛋白激素，是FBN1前体蛋白酶切后的产物。我们前期研究发现PCOS脂肪组织高表达FBN1，并伴随血清asprosin增高，其水平和雄激素存在正相关；同时初步体外实验证明重组蛋白asprosin促进前体脂肪细胞和人间充质干细胞成脂分化，并激活cAMP-PKA-CREB信号通路。据此我们提出假说：高雄激素促进PCOS脂肪组织超生理分泌asprosin，asprosin通过cAMP-PKA-CREB信号通路促进成脂分化，从而促进脂代谢异常的发生发展。本项目拟进一步通过体内外实验，阐明高雄激素促进asprosin表达以及asprosin调控成脂分化的信号通路和下游靶基因，探讨asprosin参与PCOS脂代谢的关键作用及其调控机制，为寻找新的治疗靶点提供科学依据。

脂代谢异常是多囊卵巢综合征(PCOS)最常见的远期并发症，其具体机制尚未阐明。 白脂素(asprosin)是最新发现由脂肪组织分泌的升血糖蛋白激素，是FBN1前体蛋白酶切后的产物。我们前期研究发现PCOS脂肪组织高表达asprosin，其水平和雄激素存在正相关。本项目通过过表达和敲低实验证明了asprosin促进脂肪前体细胞成脂分化，但不影响细胞增殖。通过体内外实验阐明雄激素通过雄激素受体上调asprosin的表达，从而参与调控PCOS脂代谢的发生发展，为寻找新的研究靶点提供科学依据。