Academic Journal
Increased let-7d-5p in non-alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis
| العنوان: | Increased let-7d-5p in non-alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis |
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| المؤلفون: | Infante-Menéndez, Jorge, López-Pastor, Andrea R., González-Illanes, Tamara, González-López, Paula, Huertas-Lárez, Raquel, Rey, Esther, González-Rodríguez, Águeda, García-Monzón, Carmelo, Patil, Nikita P., Vega de Céniga, Melina, Baker, Aaron B., Gómez-Hernández, Almudena, Escribano, Óscar |
| المساهمون: | Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Universidad Complutense de Madrid, Banco Santander, Instituto de Salud Carlos III, European Commission, American Heart Association, National Institutes of Health (US), Comunidad de Madrid |
| بيانات النشر: | John Wiley & Sons |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Steatosis, Insulin signalling, miRNAs, Diagnostic biomarker, Insulin resistance |
| الوصف: | [Background and Aims]: The molecular mechanisms driving non-alcoholic fatty liver disease (NAFLD) are poorly understood; however, microRNAs might play a key role in these processes. We hypothesize that let-7d- 5p could contribute to the pathophysiol-ogy of NAFLD and serve as a potential diagnostic biomarker. ; [Methods]: We evaluated let-7d- 5p levels and its targets in liver biopsies from a cross- sectional study including patients with NAFLD and healthy donors, and from a mouse model of NAFLD. Moreover, the induction of let-7d- 5p expression by fatty acids was evaluated in vitro. Further, we overexpressed let-7d- 5p in vitro to corroborate the results observed in vivo. Circulating let-7d- 5p and its potential as a NAFLD biomarker was determined in isolated extracellular vesicles from human plasma by RT-qPCR. ; [Results]: Our results demonstrate that hepatic let-7d-5p was significantly up-regulated in patients with steatosis, and this increase correlated with obesity and a decreased expression of AKT serine/threonine kinase (AKT), insulin-like growth factor 1 (IGF1), IGF-I receptor (IGF1R) and insulin receptor (INSR). These alterations were corroborated in a NAFLD mouse model. In vitro, fatty acids increased let-7d-5p expression, and its overexpression decreased AKT, IGF-IR and IR protein expression. Furthermore, let-7d-5p hindered AKT phosphorylation in vitro after insulin stimulation. Finally, circulating let-7d-5p significantly decreased in steatosis patients and receiver operating characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker. ; [Conclusions]: Our results highlight the emerging role of let-7d-5p as a potential therapeutic target for NAFLD since its overexpression impairs hepatic insulin signalling, and also, as a novel non-invasive biomarker for NAFLD diagnosis. ; This work was supported by grants RTI-2018-095098-B100 and PID2021-123076OB-I00 from the Ministerio de Ciencia, Innovación y Universidades, AENC1/22-29754 from UCM and PR75/18-21572 from Santander-UCM given to AG-H ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1478-3223 1478-3231 |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095090-B-I00/ES/ESTRATEGIAS BIOELECTROCATALITICAS PARA LA PRODUCCION Y CONVERSION DE VECTORES ENERGETICOS/; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-123076OB-I00/ES/MODULACION DE MIR-155-5P, MIR-149-5P, LET-7D-5P Y MIR-143-3P COMO APROXIMACION TERAPEUTICA PARA LA ENFERMEDAD DEL HIGADO GRASO NO ALCOHOLICO Y LA ATEROSCLEROSIS./; Publisher's version; https://doi.org/10.1111/liv.15581; Sí; Liver International 43(8): 1714-1728 (2023); http://hdl.handle.net/10261/353820 |
| DOI: | 10.1111/liv.15581 |
| الاتاحة: | http://hdl.handle.net/10261/353820 https://doi.org/10.1111/liv.15581 |
| Rights: | open |
| رقم الانضمام: | edsbas.B39CDDD4 |
| قاعدة البيانات: | BASE |
| تدمد: | 14783223 14783231 |
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| DOI: | 10.1111/liv.15581 |