Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis
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 bio...
| Autores: | , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/92257 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/92257 |
| Access Level: | acceso abierto |
| Palabra clave: | 577.2 612.015 Biología molecular (Farmacia) Bioquímica (Farmacia) 2403 Bioquímica 2302.21 Biología Molecular |
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Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosisInfante‐Menéndez, JorgeLópez‐Pastor, Andrea R.González‐Illanes, TamaraGonzález‐López, PaulaHuertas‐Lárez, RaquelRey, EstherGonzález‐Rodríguez, ÁguedaGarcía‐Monzón, CarmeloPatil, Nikita P.Vega De Céniga, MelinaBaker, Aaron B.Gómez Hernández, María De La AlmudenaEscribano Illanes, Óscar577.2612.015Biología molecular (Farmacia)Bioquímica (Farmacia)2403 Bioquímica2302.21 Biología MolecularBackground 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 corrobo-rated 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, cir-culating let-7d- 5p significantly decreased in steatosis patients and receiver operating characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker.WileyUniversidad Complutense de Madrid20232023-04-1420232023-04-14journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/92257reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengRTI-2018-095098-B100 Not available Not availablePID2021-123076OB-I00 Not available Not availableAENC1 22-29754 Not availablePR75 18-21572 Not availablePI20 00837 Not availablePI19 00123 Not available17IRG33410888 Not available Not availableW81XWH-16-1-0580 Not available Not availableW81XWH-16-1-0582 Not available Not availableR21EB023551-01 Not available Not available1R21EB024147-01A1 Not available Not available1R01HL141761-01 Not available Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/922572026-06-02T12:44:21Z |
| dc.title.none.fl_str_mv |
Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis |
| title |
Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis |
| spellingShingle |
Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis Infante‐Menéndez, Jorge 577.2 612.015 Biología molecular (Farmacia) Bioquímica (Farmacia) 2403 Bioquímica 2302.21 Biología Molecular |
| title_short |
Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis |
| title_full |
Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis |
| title_fullStr |
Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis |
| title_full_unstemmed |
Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis |
| title_sort |
Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis |
| dc.creator.none.fl_str_mv |
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, María De La Almudena Escribano Illanes, Óscar |
| author |
Infante‐Menéndez, Jorge |
| author_facet |
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, María De La Almudena Escribano Illanes, Óscar |
| author_role |
author |
| author2 |
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, María De La Almudena Escribano Illanes, Óscar |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidad Complutense de Madrid |
| dc.subject.none.fl_str_mv |
577.2 612.015 Biología molecular (Farmacia) Bioquímica (Farmacia) 2403 Bioquímica 2302.21 Biología Molecular |
| topic |
577.2 612.015 Biología molecular (Farmacia) Bioquímica (Farmacia) 2403 Bioquímica 2302.21 Biología Molecular |
| description |
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 corrobo-rated 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, cir-culating let-7d- 5p significantly decreased in steatosis patients and receiver operating characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023 2023-04-14 2023 2023-04-14 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/20.500.14352/92257 |
| url |
https://hdl.handle.net/20.500.14352/92257 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
RTI-2018-095098-B100 Not available Not available PID2021-123076OB-I00 Not available Not available AENC1 22-29754 Not available PR75 18-21572 Not available PI20 00837 Not available PI19 00123 Not available 17IRG33410888 Not available Not available W81XWH-16-1-0580 Not available Not available W81XWH-16-1-0582 Not available Not available R21EB023551-01 Not available Not available 1R21EB024147-01A1 Not available Not available 1R01HL141761-01 Not available Not available |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley |
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Wiley |
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reponame:Docta Complutense instname:Universidad Complutense de Madrid (UCM) |
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Universidad Complutense de Madrid (UCM) |
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Docta Complutense |
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