Sathyapalan Thozhukat, Hobkirk James P, Javed Zeeshan, Carroll Sean, Coady Anne-Marie, Pemberton Philip, Smith Alexander, Cianflone Katherine, Atkin Stephen L
Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Kingston upon Hull, United Kingdom.
Department of Sport, Health and Exercise Science, University of Hull, Kingston upon Hull, United Kingdom.
Front Endocrinol (Lausanne). 2019 Jun 25;10:394. doi: 10.3389/fendo.2019.00394. eCollection 2019.
Atorvastatin has been shown to improve cardiovascular risk (CVR) indices in women with polycystic ovary syndrome (PCOS). Low-grade chronic inflammation of adipose tissue may link PCOS and adverse CVR. In pro-inflammatory states such as PCOS, spontaneous activation of the alternative pathway of complement results in increased generation of acylation stimulating protein (ASP) from adipocytes irrespective of body mass index. The objective of this study was to determine the effect of atorvastatin on markers of adipose tissue dysfunction and inflammation; acylation-stimulating-protein (ASP), interleukin-6 (IL-6), and monocyte-chemoattractant-protein-1 (MCP-1) in PCOS. This was a randomized, double-blind, placebo-controlled study where 40 medication-naive women with PCOS and biochemical hyperandrogenaemia were randomized to either atorvastatin 20 mg daily or placebo for 12 weeks. Following the 12 week randomization; both group of women with PCOS were subsequently started on metformin 1,500 mg daily for further 12 weeks to assess whether pre-treatment with atorvastatin potentiates the effects of metformin on markers of adipose tissue function We conducted a review to detect plasma ASP and the pro-inflammatory cytokines IL6 and MCP-1 before and after 12 and 24 weeks of treatment. There was significant reduction in ASP (156.7 ± 16.2 vs. 124.4 ± 14.8 ng/ml p <0.01), IL-6 (1.48 ± 0.29 vs.0.73 ± 0.34 pg/ml = 0.01) and MCP-1 (30.4 ± 4.2 vs. 23.0 ± 4.5 pg/ml = 0.02) after 12 weeks of atorvastatin that was maintained subsequently with 12 weeks treatment with metformin. There was a significant positive correlation between ASP levels with CRP ( < 0.01), testosterone ( < 0.01) and HOMA-IR ( < 0.01); IL-6 levels with CRP (p <0.01) and testosterone ( < 0.01) and MCP-1 with CRP ( < 0.01); testosterone ( < 0.01) and HOMA-IR ( < 0.02). This analysis revealed that 12 weeks of atorvastatin treatment significantly decreased the markers of adipose tissue dysfunction and inflammation, namely ASP, IL-6 and MCP-1 in obese women with PCOS. Changes in adipose tissue markers were significantly associative with substantial improvements in HOMA-IR, testosterone and hs-CRP levels. ISRCTN24474824.
阿托伐他汀已被证明可改善多囊卵巢综合征（PCOS）女性的心血管风险（CVR）指标。脂肪组织的低度慢性炎症可能与PCOS和不良CVR相关。在PCOS等促炎状态下，补体替代途径的自发激活会导致无论体重指数如何，脂肪细胞中酰化刺激蛋白（ASP）的生成增加。本研究的目的是确定阿托伐他汀对PCOS患者脂肪组织功能障碍和炎症标志物（酰化刺激蛋白（ASP）、白细胞介素-6（IL-6）和单核细胞趋化蛋白-1（MCP-1））的影响。这是一项随机、双盲、安慰剂对照研究，40名未接受过药物治疗的PCOS和生化性高雄激素血症女性被随机分为每天服用20毫克阿托伐他汀组或安慰剂组，为期12周。在12周随机分组后，两组PCOS女性随后均开始每天服用1500毫克二甲双胍，持续12周，以评估阿托伐他汀预处理是否能增强二甲双胍对脂肪组织功能标志物的作用。我们进行了一项回顾性研究，以检测治疗12周和24周前后血浆ASP以及促炎细胞因子IL-6和MCP-1的水平。阿托伐他汀治疗12周后，ASP（156.7±16.2 vs. 124.4±14.8 ng/ml，p<0.01）、IL-6（1.48±0.29 vs.0.73±0.34 pg/ml，p = 0.01）和MCP-1（30.4±4.2 vs. 23.0±4.5 pg/ml，p = 0.02）显著降低，随后在服用二甲双胍12周的治疗中维持这一效果。ASP水平与CRP（p<0.01）、睾酮（p<0.01）和HOMA-IR（p<0.01）之间存在显著正相关；IL-6水平与CRP（p<0.01）和睾酮（p<0.01）以及MCP-1与CRP（p<0.01）、睾酮（p<0.01）和HOMA-IR（p<0.02）之间存在显著正相关。该分析表明，12周的阿托伐他汀治疗显著降低了肥胖PCOS女性脂肪组织功能障碍和炎症的标志物，即ASP、IL-6和MCP-1。脂肪组织标志物的变化与HOMA-IR、睾酮和hs-CRP水平的显著改善显著相关。ISRCTN24474824。
