Zhou Xin, Wang Yanping, Chen Wenyun, Zhang Hongmin, He Yirui, Dai Han, Hu Wenjing, Li Ke, Zhang Lili, Chen Chen, Yang Gangyi, Li Ling
The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400042, China.
Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
J Clin Med. 2023 Jan 22;12(3):888. doi: 10.3390/jcm12030888.
Serum human hedgehog-interacting protein (HHIP) concentration is associated with diabetes. However, the relationship between HHIP and polycystic ovary syndrome (PCOS) or abnormal sex hormones remains unknown. This study was an observational cross-sectional study, with additional short-term intervention studies and follow-up studies. Bioinformatics analysis was performed to explore the association of PCOS with metabolic-related genes and signaling pathways. OGTT and EHC were performed on all participants. Lipid infusion, cold exposure, and 45-min treadmill test were performed on all healthy women. A total of 137 women with PCOS were treated with metformin, GLP-1RA, or TZDs for 24 weeks. Serum HHIP levels were higher in insulin resistance (IR) and PCOS women. Circulating HHIP levels were significantly correlated with adiponectin (Adipoq) levels, obesity, IR, and metabolic indicators. A correlation presented between HHIP and DHEA-S, FAI, SHBG, and FSH. Serum HHIP levels were significantly elevated by oral glucose challenge in healthy women, but not affected by EHC. Lipid infusion decreased serum HHIP levels, while cold exposure increased HHIP levels in healthy women. GLP-1RA and TZD treatment reduced serum HHIP levels in PCOS women, while metformin treatment did not affect HHIP levels. HHIP may be a useful biomarker and novel drug target for PCOS and IR individuals.
血清人刺猬因子相互作用蛋白（HHIP）浓度与糖尿病相关。然而，HHIP与多囊卵巢综合征（PCOS）或性激素异常之间的关系尚不清楚。本研究为观察性横断面研究，并附加了短期干预研究和随访研究。进行生物信息学分析以探索PCOS与代谢相关基因及信号通路的关联。对所有参与者进行口服葡萄糖耐量试验（OGTT）和冷加压试验（EHC）。对所有健康女性进行脂质输注、冷暴露和45分钟跑步机测试。共有137名PCOS女性接受二甲双胍、胰高血糖素样肽-1受体激动剂（GLP-1RA）或噻唑烷二酮类药物（TZDs）治疗24周。胰岛素抵抗（IR）和PCOS女性的血清HHIP水平较高。循环HHIP水平与脂联素（Adipoq）水平、肥胖、IR及代谢指标显著相关。HHIP与硫酸脱氢表雄酮（DHEA-S）、游离雄激素指数（FAI）、性激素结合球蛋白（SHBG）和促卵泡生成素（FSH）之间存在相关性。口服葡萄糖激发试验可使健康女性血清HHIP水平显著升高，但不受EHC影响。脂质输注可降低健康女性血清HHIP水平，而冷暴露可使其升高。GLP-1RA和TZDs治疗可降低PCOS女性血清HHIP水平，而二甲双胍治疗不影响HHIP水平。HHIP可能是PCOS和IR个体的有用生物标志物及新型药物靶点。
