ECE2017 Eposter Presentations: Diabetes, Obesity and Metabolism Obesity (81 abstracts)
Associations between the dysregulation of splicing machinery components and the development of hepatic steatosis in obese women
Mercedes del Río-Moreno 1 , Sergio Pedraza-Arévalo 1 , Sandra González-Rubio 2 , Gustavo Ferrín 2 , Manuel Rodríguez-Perálvarez 2 , Rhonda D Kineman 3 , Alejandro Ibáñez-Costa 1 , Manuel de la Mata 2 , Justo P Castaño 1 , Raúl M Luque 1 & Manuel D Gahete 1
1Maimonides Institute of Biomedical Research of Cordoba (IMIBIC); Reina Sofia University Hospital (HURS); Department of Cell Biology, Physiology and Immunology, University of Cordoba (UCO); CIBER Physi, Cordoba, Spain; 2Department of Hepatology and Liver Transplantation, HURS/IMIBIC; CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Cordoba, Spain; 3Research and Development Division, Jesse Brown Veterans Affairs Medical Center and Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, Illinois, USA.
: Hepatic steatosis is a common obesity-associated pathology characterized by the accumulation of fat within the liver, which can progress to liver fibrosis, cirrhosis and ultimately lead to hepatocellular carcinoma. Remarkably, obesity and cancer course with a profound dysregulation of the genetic expression patterns and, particularly, with the aberrant expression of splicing variants that could contribute to the aggressiveness and comorbidities of these pathologies. Since the appearance of alternative splicing variants could be related to a dysregulation of the cellular machinery responsible for this process ((spliceosome core elements and splicing factors (SFs)), the objective of the present study was to determine the association between the expression pattern of the components of this machinery and hepatic steatosis of obese patients. To this end, we collected clinical and demographic data and liver biopsy samples from obese women (IMC>30) with (n=32) and without (n=9) hepatic steatosis. RNA from liver samples was extracted and retrotranscribed to determine the expression levels of selected components of the major (n=13) and minor spliceosome (n=4), and associated SFs (n=28) using a qPCR-based array. Results revealed that the liver of steatotic patients exhibit a profound dysregulation of certain spliceosome components and SFs compared to non-steatotic patients (e.g. RNU6, SF3b1, etc.). Although these alterations were not associated with the hepatic steatosis level, the expression pattern of the components of this cellular machinery could define discrete groups of steatotic patients that presented similar alterations in certain spliceosome components and SFs. Interestingly, these groups of patients were also characterized by particular hepatic and clinical-metabolic alterations (e.g. ALT, hyperglicemia, hyperinsulinemia, etc.). Therefore, although further confirmatory studies are needed, these results could suggest that the development of hepatic steatosis and its associated comorbidities could be linked to the dysregulation of certain components of the splicing machinery, which may provide novel diagnostic/therapeutic tools for this pathology.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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