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Dysregulation of the FGF21-adiponectin axis in a large cohort of patients with severe obesity and liver disease
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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.
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CASTAÑÉ VILAFRANCA, Helena, et al. Dysregulation of the FGF21-adiponectin axis in a large cohort of patients with severe obesity and liver disease. International Journal of Molecular Sciences. 2025. Vol. 26, núm. 17, pàgs. 8510. ISSN 1422-0067. [consulta: 8 de maig de 2026]. Disponible a: https://hdl.handle.net/2445/223588