■多囊卵巢综合征(PCOS)通常与代谢相关的脂肪肝(MAFLD)有关。MAFLD与肝功能改变有关,全身代谢异常,和称为有机因子的信号分子的异常循环水平。这里,我们评估了两种随机治疗对PCOS和无肥胖的青春期女孩的一组有机因子的影响。并报告与肝损伤循环生物标志物的关联,在上述研究中作为安全标记进行了纵向评估。
■肝酶[天冬氨酸氨基转移酶(AST),丙氨酸氨基转移酶(ALT),在之前的随机试验研究中,将口服避孕药(OC)与低剂量联合使用螺内酯-吡格列酮-二甲双胍(spiomet)1年的效果进行了比较,并将γ-谷氨酰转移酶(GGT)]作为安全性标志物进行了评估.作为后临时端点,有机因子成纤维细胞生长因子-21(FGF21),地西泮结合蛋白-1(DBI),在OC(N=26)或spiomet(N=28)治疗6个月后,通过ELISA评估和流蛋白样蛋白(METRNL)。辅助,内分泌代谢,身体成分(使用DXA),还评估了腹部脂肪分区(使用MRI)。健康,年龄匹配的青春期女孩(N=17)作为对照。
■OC治疗期间循环ALT和GGT水平增加,并在治疗后阶段恢复到基线浓度;相反,spiomet治疗未引起ALT和GGT浓度的可检测变化。关于治疗6个月后的有机因子,(1)PCOS青少年的FGF21水平明显高于对照女孩;(2)接受OC治疗的女孩的DBI水平低于对照组和接受spiomet治疗的女孩;(3)PCOS女孩和对照组之间的METRNL浓度无差异。仅在接受OC治疗的女孩中,血清ALT和GGT水平与循环METRNL水平直接相关(分别为R=0.449,P=0.036和R=0.552,P=0.004)。
■仅在接受OC治疗的女孩中出现的ALT和GGT水平的增加与循环METRNL水平有关,提示METRNL合成增强是对OC治疗引起的肝脏变化的反应。
■https://doi.org,标识符10.1186/ISRCTN29234515、10.1186/ISRCTN11062950。
UNASSIGNED: 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.
UNASSIGNED: 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 post hoc 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: https://doi.org, identifiers 10.1186/ISRCTN29234515, 10.1186/ISRCTN11062950.