ECE2018 Guided Posters Adrenal clinical (10 abstracts)
Metabolic fingerprints after Cushing syndrome cure
Guillermo Garcia-Eguren 1 , Pedro Vizan 2 , Mar Gonzalez 2 , Enrique Blanco 2 , Marina Rojo 1 , Mireia Mora 1, , Oriol Giró 1 , Irene Halperin 1, , Luciano Di Croce 2 & Felicia A Hanzu 1,
1Laboratory of Endocrine Disorders IDIBAPS/CIBERDEM, Barcelona, Spain; 2Center of Genomic Regulation, Barcelona, Spain; 3Endocrinology Department Hospital Clinic, Barcelona, Spain.
Introduction: Active hypercortisolism of Cushing syndrome (CS) determines major changes in the plasticity and function of metabolic key target tissues as the adipose tissue (AT). Persistence of target tissue altered metabolic memory after the cure/remission of Cushing syndrome is still at debate as clinical observational studies are limited due to confounder factors both in endogenous as exogenous CS. We postulate that after remission of hypercortisolism, adipose tissue (AT) present persistent deregulations for a long time after the cure of CS contributing to the maintaining of a metabolic syndrome-like phenotype and an increased cardiovascular risk. The aim of this study was to investigate the metabolic phenotype and the adipose tissue after the cure of CS employing an established reversible CS animal model (doi: 10.1073/pnas.1323681111).
Methods: Prospective study in animal C57BL/6 mice with reversible CS studied in active hypercortisolism and after the reversion to eucortisolism. Groups: j). Mice with active CS (ACS) induced by oral chronic treatment with glucocorticoids (GC); (jj). Mice with obesity induced by hypercaloric diet (HCD); (jjj). Controls (CTR). Mice from group’s j and jj received treatment (GC vs. HCD) during 5 weeks (W). All animals were metabolically and hormonal phenotyped at treatment end (at 5W) and at 15W. Adipose tissue distribution (MRI), plasticity (histology) and function (RNAseq, rt-PCR, cytokine arrays) were analyzed in all groups.
Results: GC treated mice presented after 5W of treatment the complete CS phenotype. Reversible CS mice (RCS) presented at 15W after the end of the active treatment no significant changes in body weight but an increase in white adipose tissue (WAT) (P<0.005), and marked insulin resistance (HOMA-IR: P<0.05 and ITT: P<0.01) as respect to CTR and HCD. WAT of RCS presented low turnover, hypertrophic adipocytes (P<0.05). Heat map, PCA and t-SNE analysis and the persistence of 488 up- and 388 down- regulated genes between active ACS and RCS indicate profound alterations of WAT in RCS mice. Genes validation, pathway and adipocytokines analysis are in process.
Conclusion: This is the first study in a murine animal model reporting the persistence of an altered metabolic phenotype marked by insulin resistance and changes in the adipose tissue plasticity after cure of CS.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more