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Elevated chemerin induces insulin resistance in human granulosa‐lutein cells from polycystic ovary syndrome patients
Author(s) -
Li Xiaoxue,
Zhu Qinling,
Wang Wangsheng,
Qi Jia,
He Yaqiong,
Wang Yuan,
Lu Yao,
Wu Hasiximuke,
Ding Ying,
Sun Yun
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201802829r
Subject(s) - chemerin , polycystic ovary , insulin resistance , medicine , endocrinology , irs1 , adipokine , insulin receptor , biology , insulin
The insulin resistance (IR) of ovarian granulosa cells from polycystic ovary syndrome (PCOS) aggravates the abnormalities in steroidogenesis and anovulation, and chemerin is an adipokine involved in regulating adipogenesis and glucose homeostasis. The role and underlying mechanism of chemerin in developing IR of the granulosa cells from PCOS remain unclear. Plasma, follicular fluid, and human granulosa‐lutein cells (hGLs) were collected from non‐PCOS and patients with PCOS with or without IR. The chemerin levels were elevated in both follicular fluid and hGL samples from patients with PCOS with IR, and the hGLs from patients with PCOS with IR showed decreased insulin sensitivity and impaired glucose uptake capacity. Moreover, treatment of chemerin attenuated insulin‐stimulated glucose uptake by decreasing phosphorylation of insulin receptor substrate (IRS)1/2 Tyr612, phosphorylation of protein kinase B Ser473, and membrane translocation of glucose transporter type 4 through increasing Ser307 phosphorylation of IRS1 in cultured hGLs. These effects could be abolished by small interfering RNA‐mediated knockdown of chemokine‐like receptor 1. Furthermore, insulin induced the expression of chemerin in hGLs. Our findings demonstrate a novel role of chemerin in the metabolic dysfunction of PCOS, which suggested that chemerin and its receptor can be further implicated as potential therapeutic targets in the future treatment of PCOS.—Li, X., Zhu, Q., Wang, W., Qi, J., He, Y., Wang, Y., Lu, Y., Wu, H., Ding, Y., Sun, Y. Elevated chemerin induces insulin resistance in human granulosa‐lutein cells from polycystic ovary syndrome patients. FASEB J. 33, 11303–11313 (2019). www.fasebj.org