Elevated SAA1 promotes the development of insulin resistance in ovarian granulosa cells in polycystic ovary syndrome

Reproductive Biology and Endocrinology

Yuan Wang¹  Yanzhi Du¹  Qinling Zhu¹  Ying Ding¹  Yue Yao¹  Yao Lu¹  Jia Qi¹  Hanting Zhao¹  Yaqiong He¹  Hasiximuke Wu¹  Jiaan Huang¹  Wangsheng Wang¹  Kang Sun¹  Lizhen Xu¹  Yun Sun¹  Xinyu Li¹ 

[1] Center for Reproductive Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200135, Shanghai, People’s Republic of China;Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, 200135, Shanghai, People’s Republic of China;

关键词: Serum amyloid A1;    Polycystic ovary syndrome;    Insulin resistance;    Granulosa cells;    Inflammation;   

DOI  :  10.1186/s12958-021-00873-3

来源: Springer

【 摘 要 】

BackgroundInsulin resistance (IR) contributes to ovarian dysfunctions in polycystic ovarian syndrome (PCOS) patients. Serum amyloid A1 (SAA1) is an acute phase protein produced primarily by the liver in response to inflammation. In addition to its role in inflammation, SAA1 may participate in IR development in peripheral tissues. Yet, expressional regulation of SAA1 in the ovary and its role in the pathogenesis of ovarian IR in PCOS remain elusive.MethodsFollicular fluid, granulosa cells and peripheral venous blood were collected from PCOS and non-PCOS patients with and without IR to measure SAA1 abundance for analysis of its correlation with IR status. The effects of SAA1 on its own expression and insulin signaling pathway were investigated in cultured primary granulosa cells.ResultsOvarian granulosa cells were capable of producing SAA1, which could be induced by SAA1 per se. Moreover, the abundance of SAA1 significantly increased in granulosa cells and follicular fluid in PCOS patients with IR. SAA1 treatment significantly attenuated insulin-stimulated membrane translocation of glucose transporter 4 and glucose uptake in granulosa cells through induction of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression with subsequent inhibition of Akt phosphorylation. These effects of SAA1 could be blocked by inhibitors for toll-like receptors 2/4 (TLR 2/4) and nuclear factor kappa light chain enhancer of activated B (NF-κB).ConclusionsHuman granulosa cells are capable of feedforward production of SAA1, which significantly increased in PCOS patients with IR. Excessive SAA1 reduces insulin sensitivity in granulosa cells via induction of PTEN and subsequent inhibition of Akt phosphorylation upon activation of TLR2/4 and NF-κB pathway. These findings highlight that elevation of SAA1 in the ovary promotes the development of IR in granulosa cells of PCOS patients.

【 授权许可】

CC BY