Endocrinology Department, Institut de Recerca Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
Front Endocrinol (Lausanne). 2024 May 16;15:1325230. doi: 10.3389/fendo.2024.1325230. eCollection 2024.
Polycystic ovary syndrome (PCOS) is often associated with metabolic-associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function, systemic dysmetabolism, and abnormal circulating levels of signaling molecules called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage, which were assessed longitudinally in the aforementioned studies as safety markers.
Liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) with those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 year. As a endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI), and meteorin-like protein (METRNL) were assessed by ELISA after 6 months of OC (N = 26) or spiomet (N = 28). Auxological, endocrine-metabolic, body composition (using DXA), and abdominal fat partitioning (using MRI) were also evaluated. Healthy, age-matched adolescent girls (N = 17) served as controls.
Circulating ALT and GGT levels increased during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 months of treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls than in controls and spiomet-treated girls; and (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels were directly correlated with circulating METRNL levels only in OC-treated girls (R = 0.449, P = 0.036 and R = 0.552, P = 0.004, respectively).
The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls is associated with circulating METRNL levels, suggesting enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment.
https://doi.org, identifiers 10.1186/ISRCTN29234515, 10.1186/ISRCTN11062950.
多囊卵巢综合征（PCOS）常与代谢相关脂肪性肝病（MAFLD）相关。MAFLD 与肝功能改变、全身代谢紊乱以及称为器官因子的信号分子的循环水平异常有关。在这里，我们评估了两种随机治疗方法对一组无肥胖青少年 PCOS 患者的器官因子的影响，并报告了与循环肝损伤生物标志物的关联，这些标志物在上述研究中作为安全性标志物进行了纵向评估。
在先前的两项比较口服避孕药（OC）和低剂量螺内酯-吡格列酮-二甲双胍（spiomet）治疗 1 年的随机试验中，我们将天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）和γ-谷氨酰转移酶（GGT）作为安全性标志物进行了评估。作为一个终点，我们通过 ELISA 评估了治疗 6 个月后的成纤维细胞生长因子 21（FGF21）、地西泮结合蛋白-1（DBI）和流星样蛋白（METRNL）等器官因子。还评估了人体测量、内分泌代谢、身体成分（使用 DXA）和腹部脂肪分布（使用 MRI）。年龄匹配的健康青少年女孩（N=17）作为对照组。
OC 治疗期间循环 ALT 和 GGT 水平升高，并在治疗后阶段恢复到基线浓度；相反，spiomet 治疗未检测到 ALT 和 GGT 浓度的变化。关于治疗 6 个月后的器官因子，（1）PCOS 青少年的 FGF21 水平明显高于对照组女孩；（2）OC 治疗组女孩的 DBI 水平低于对照组和 spiomet 治疗组女孩；（3）PCOS 女孩和对照组女孩之间的 METRNL 浓度没有差异。仅在 OC 治疗组女孩中，血清 ALT 和 GGT 水平与循环 METRNL 水平呈直接相关（R=0.449，P=0.036 和 R=0.552，P=0.004）。
仅在 OC 治疗组女孩中发生的治疗期间 ALT 和 GGT 水平升高与循环 METRNL 水平相关，表明 METRNL 合成增加是 OC 治疗引起的肝变化的反应。
https://doi.org，标识符 10.1186/ISRCTN29234515，10.1186/ISRCTN11062950。
