RT Journal Article
T1 Increased let‐7d‐5p in non‐alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis
A1 Infante‐Menéndez, Jorge
A1 López‐Pastor, Andrea R.
A1 González‐Illanes, Tamara
A1 González‐López, Paula
A1 Huertas‐Lárez, Raquel
A1 Rey, Esther
A1 González‐Rodríguez, Águeda
A1 García‐Monzón, Carmelo
A1 Patil, Nikita P.
A1 Vega De Céniga, Melina
A1 Baker, Aaron B.
A1 Gómez Hernández, María De La Almudena
A1 Escribano Illanes, Óscar
AB 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.
PB Wiley
SN 1478-3223
SN 1478-3231
YR 2023
FD 2023-04-14
LK https://hdl.handle.net/20.500.14352/92257
UL https://hdl.handle.net/20.500.14352/92257
LA eng
NO Infante-Menéndez J, López-Pastor AR, González-Illanes T, González-López P, Huertas-Lárez R, Rey E, González-Rodríguez Á, García-Monzón C, Patil NP, Vega de Céniga M, Baker AB, Gómez-Hernández A, Escribano O. Increased let-7d-5p in non-alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis. Liver Int. 2023 Aug;43(8):1714-1728. doi: 10.1111/liv.15581. Epub 2023 Apr 14. PMID: 37057737; PMCID: PMC10523911.
NO Ministerio de Ciencia, Innovación y Universidades
NO Santander-UCM
NO UCM
NO Instituto de Salud Carlos III
NO Fondo Europeo para el Desarrollo Regional (FEDER)
NO American Heart Association
NO DOD CDMRP
NO National Institutes of Health
DS Docta Complutense
RD 6 abr 2025