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大量重度肥胖和肝病患者队列中FGF21-脂联素轴的失调

Dysregulation of the FGF21-Adiponectin Axis in a Large Cohort of Patients with Severe Obesity and Liver Disease.

作者信息

Castañé Helena, Jiménez-Franco Andrea, Onoiu Alina-Iuliana, Cambra-Cortés Vicente, Hernández-Aguilera Anna, Parada David, Riu Francesc, Zorzano Antonio, Camps Jordi, Joven Jorge

机构信息

Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, 43204 Reus, Spain.

Department of Pathology, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, 43204 Reus, Spain.

出版信息

Int J Mol Sci. 2025 Sep 2;26(17):8510. doi: 10.3390/ijms26178510.

DOI:10.3390/ijms26178510
PMID:40943431
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12429463/
Abstract

We investigated the impact of liver damage on systemic inter-organ communication in an extensive observational case-control study of 923 patients with severe obesity and biopsy-confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH) undergoing bariatric surgery. Using a comprehensive panel of circulating organokines, including fibroblast growth factor (FGF) 19, FGF21, adiponectin, galectin-3, irisin, and leptin, along with choline metabolites, we characterized metabolic signaling patterns associated with liver disease severity. Compared to controls, patients with MASLD/MASH exhibited significantly lower levels of FGF19, choline, and trimethylamine, while FGF21, galectin-3, irisin, and leptin were elevated. Sex-specific alterations in leptin and adiponectin were observed in patients with severe obesity but not in controls. Network analysis revealed a complex and individualized interplay among organokines, shaped by age, sex, and anthropometric factors. Despite this complexity, a dysregulation of the FGF21-adiponectin axis was associated with more advanced liver involvement. The large cohort and comprehensive organokine profiling studied provide valuable insights into the role of the FGF21-adiponectin axis on systemic metabolic alterations in severe obesity and their potential clinical implications.

摘要

在一项针对923例重度肥胖且经活检确诊为代谢功能障碍相关脂肪性肝病（MASLD）或代谢功能障碍相关脂肪性肝炎（MASH）并接受减肥手术患者的广泛观察性病例对照研究中，我们调查了肝脏损伤对全身器官间通讯的影响。我们使用了一组全面的循环器官因子，包括成纤维细胞生长因子（FGF）19、FGF21、脂联素、半乳糖凝集素-3、鸢尾素和瘦素，以及胆碱代谢物，来表征与肝病严重程度相关的代谢信号模式。与对照组相比，MASLD/MASH患者的FGF19、胆碱和三甲胺水平显著降低，而FGF21、半乳糖凝集素-3、鸢尾素和瘦素水平升高。在重度肥胖患者中观察到瘦素和脂联素的性别特异性改变，但在对照组中未观察到。网络分析揭示了器官因子之间复杂且个体化的相互作用，这种相互作用受年龄、性别和人体测量因素影响。尽管存在这种复杂性，但FGF21-脂联素轴的失调与更严重的肝脏受累相关。所研究的大型队列和全面的器官因子分析为FGF21-脂联素轴在重度肥胖患者全身代谢改变中的作用及其潜在临床意义提供了有价值的见解。

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