ECE2019 Guided Posters Adrenal and Neuroendocrine - Basic (14 abstracts)
Gene expression changes in visceral adipose tissue of Cushing syndrome.
Guillermo Garcia-Eguren 1 , Mar Gonzalez 2 , Enrique Blanco 2 , Oriol Giro 1 , Oscar Vidal 3 , Francesc Carmona 3 , Gregori Casals 3 , Mireia Mora 3 , Irene Halperin 3 , Luciano diCroce 2 & Felicia A Hanzu 3
1IDIBAPS, Barcelona, Spain; 2CRG, Barcelona, Spain; 3HCB, Barcelona, Spain.
Introduction: Visceral adipose tissue (VAT) is the key target tissue of glucocorticoids (GC) during active Cushing Syndrome (CS) and a metabolic tissue associated to insulin-resistance and an increased cardiometabolic risk. Till date there are no data regarding gene expression in VAT in CS and only few data about the mRNA in subcutaneous one. The aim of this study was to study the visceral VAT tissue transcriptional changes in ACTH-independent CS.
Methods: 7 ACTH-independent CS patients due to adrenal cortical adenomas diagnosed in our hospital during the last 3 years and 14 sex (3m/4w), age (32–60y), BMI (29.1±0.5 kg/m2), cardiovascular and metabolic comorbidities matched controls (CTR) were included in the study. Clinical and analytical phenotype data were obtained prior to surgery. VAT (omentum) was collected after overnight fasting during the laparoscopic abdominal, programmed surgery. VAT plasticity (histology, immunochemistry) and function (RNAseq, rt-PCR) were analyzed. Differentially (up and down, P*<0.05) expressed genes in CS and CTR were compared and genes identified. RT-PCR was performed to validate the results and pathway analysis is ongoing.
Results: VAT of patients with active CS presented increased hypertrophic adipocytes and macrophage infiltration independent of the associated comorbidities. Heat map, PCA and t-SNE analysis and RT-PCR validation showed 10 up and 18 down regulated genes involved in macrophage activation, adipogenesis, insulin-signaling and lipid metabolism. Analysis of the overall gene changes network and relationship with the CS hormonal and phenotype characteristics are in process.
Conclusion: This is the first study providing insights to tissue transcriptomic changes in VAT of CS that may be have a causative effect on the comorbidities associated with the chronic hypercortisolism.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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