ECE2016 Guided Posters Obesity (10 abstracts)
The liver of obese patients with hepatic steatosis exhibits a severe dysregulation of key splicing machinery components as compared to obese patients without hepatic steatosis
Mercedes del Río-Moreno 1 , Sergio Pedraza-Arévalo 1 , Sandra González-Rubio 2 , Gustavo Ferrín 2 , Manuel D Gahete 1 , Manuel Rodríguez-Perálvarez 2 , Rhonda D Kineman 3 , Alejandro Ibañez-Costa 1 , Manuel de la Mata 2 , Justo P Castaño 1 & Raúl M Luque 1
1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Hospital Universitario Reina Sofía (HURS), Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), CIBERobn, Córdoba, Spain; 2Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC. CIBERehd, Córdoba, 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.
Obesity, a disease that is growing at epidemic proportions worldwide, is caused by a combination of genetic and lifestyle factors. One of the most common pathologies associated with obesity is hepatic steatosis, an accumulation of fat within the liver that can progress to liver fibrosis, cirrhosis, and ultimately lead to hepatocellular carcinoma. There is emerging evidence that alternative mRNA splicing, the key mechanism providing transcript and protein diversity, is dysregulated in many tissues under adverse metabolic conditions, such as obesity and cancer. Moreover, the splicing variants generated within this process could contribute to the aggressiveness and comorbidities of these diseases. We hypothesized that an alteration in the splicing machinery could occur in obese patients with hepatic steatosis, which might ultimately be associated with the progression to hepatic fibrosis/cirrhosis/carcinoma. To address this question, an array of selected components of the major (n=13) and minor spliceosome (n=4), and associated splicing factors (n=28) was developed, and their expression levels were evaluated using a Fluidigm methodology, in a series of liver samples from obese (BMI >30) women with (n=33) and without (n=9) liver steatosis. Results revealed that expression of a number of relevant splicing factors (SRSF2, SND1, SRRM1, PTBP1, KHDRBS1) and spliceosome components (SF3Btv2, U2AF1, U2AF2, RNU6) was altered in steatosis vs non-steatosis liver tissues. Interestingly, some of these changes were associated with relevant clinical parameters, including glucose levels (i.e. SRSF2, U2AF1/2, KHDRBS1), gamma-glutamyltransferase (SRSF2, U2AF1, KHDRBS1), HDL (U2AF2, SND1) as well as with insulin, cholesterol, creatinine and HOMA-IR (i.e. RNU6). Finally, ROC analysis revealed that the expression of specific splicing factors, especially SRSF2, U2AF2, PTBP1 and RNU6, can clearly predict patients with or without hepatic steatosis. In conclusion, the expression of specific splicing machinery components is significantly altered in the liver of obese patients with hepatic steatosis. Ongoing studies would clarify the potential pathological implications of these findings, which could help to predict a worsening in steatosis, and may provide novel diagnostic biomarkers and therapeutic tools for this disease.
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