Daniela Díaz-Catalán, Júlia Capó, Arturo Vega-Beyhart, Maite Rodrigo, Mireia Mora, Oscar Vidal, Mattia Squarcia, Joaquim Enseñat, Gregori Casals, Felicia Hanzu
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引用次数: 0
Abstract
Background: Cushing's Syndrome (CS) results from prolonged exposure to excessive glucocorticoids (GCs), leading to metabolic disturbances and adrenal insufficiency (AI). Fibroblast growth factor 21 (FGF21) has shown promise as a potential therapeutic target for metabolic disorders. This study explores the effects of FGF21 on adrenal gland function in a mouse model of AI following chronic hypercortisolism and investigates sex-dependent differences in the hypothalamic-pituitary-adrenal (HPA) axis response.
Methods: We employed a mouse model of AI after chronic corticosterone (CORT) treatment. We studied the effects of recombinant human FGF21 (hFGF21) administration on adrenal function in AI mice. We then investigated male and female wild-type (WT) and FGF21-overexpressing transgenic (Tg) mice subjected to 5 weeks of CORT treatment reaching CS phenotype, followed by immediate analysis or a 10-week recovery period. We evaluated metabolic parameters, HPA axis function, and adrenal gland morphology and gene expression.
Results: Prolonged CORT exposure resulted in metabolic disturbances and HPA axis dysregulation. hFGF21 treatment increased CORT and ACTH secretion in AI mice. FGF21 overexpression influenced glucose homeostasis and insulin regulation during CORT treatment and recovery, with sex-specific effects. Tissue-specific regulation of Klb expression was observed across the HPA axis, with distinct patterns between males and females. Tg mice displayed altered adrenal progenitor cell activation and steroidogenic gene expression. Sex-specific differences were observed in adrenal capsule remodeling and gene expression patterns during recovery.
Conclusions: This study reveals the complex interplay between FGF21 signaling and GC-induced metabolic and endocrine changes, suggesting a potential sex-specific role of FGF21 in the metabolic and HPA after CS.
期刊介绍：
Molecular Metabolism is a leading journal dedicated to sharing groundbreaking discoveries in the field of energy homeostasis and the underlying factors of metabolic disorders. These disorders include obesity, diabetes, cardiovascular disease, and cancer. Our journal focuses on publishing research driven by hypotheses and conducted to the highest standards, aiming to provide a mechanistic understanding of energy homeostasis-related behavior, physiology, and dysfunction.
We promote interdisciplinary science, covering a broad range of approaches from molecules to humans throughout the lifespan. Our goal is to contribute to transformative research in metabolism, which has the potential to revolutionize the field. By enabling progress in the prognosis, prevention, and ultimately the cure of metabolic disorders and their long-term complications, our journal seeks to better the future of health and well-being.
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