RT Journal Article
T1 miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset
A1 Sanchez-Ceinos, Julia
A1 Rangel-Zuniga, Oriol A.
A1 Clemente-Postigo, Mercedes
A1 Podadera-Herreros, Alicia
A1 Camargo, Antonio
A1 Francisco Alcala-Diaz, Juan
A1 Guzman-Ruiz, Rocio
A1 Lopez-Miranda, Jose
A1 Malagon, Maria M.
K1 Insulin-resistance
K1 Circulating mirnas
K1 Oxidative stress
K1 Glucose-uptake
K1 Obesity
K1 Adipocytes
K1 Expression
K1 Micrornas
K1 Intervention
K1 Activation
AB Circulating microRNAs (miRNAs) have been proposed as biomarkers for type 2 diabetes (T2D). Adipose tissue (AT), for which dysfunction is widely associated with T2D development, has been reported as a major source of circulating miRNAs. However, the role of dysfunctional AT in the altered pattern of circulating miRNAs associated with T2D onset remains unexplored. Herein, we investigated the relationship between T2D-associated circulating miRNAs and AT function, as well as the role of preadipocytes and adipocytes as secreting cells of candidate circulating miRNAs. Among the plasma miRNAs related to T2D onset in the CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) cohort, baseline miR-223-3p levels (diminished in patients who next developed T2D [incident-T2D]) were significantly related to AT insulin resistance (IR). Baseline serum from incident-T2D participants induced inflammation and IR in 3T3-L1 adipocytes. We demonstrated that tumor necrosis factor (TNF)-alpha inhibited miR-223-3p secretion while enhancing miR-223-3p intracellular accumulation in 3T3-L1 (pre)adipocytes. Overexpression studies showed that an intracellular increase of miR-223-3p impaired glucose and lipid metabolism in these cells. Our findings provide mechanistic insights into the alteration of circulating miRNAs preceding T2D, unveiling both preadipocytes and adipocytes as miR-223-3p-secreting cells and suggesting that inflammation promotes miR-223-3p intracellular accumulation, which might contribute to (pre)adipocyte dysfunction and body metabolic dysregulation.
PB Cell press
SN 2162-2531
YR 2021
FD 2021-01-14
LK http://hdl.handle.net/10668/18859
UL http://hdl.handle.net/10668/18859
LA en
NO Sánchez-Ceinos J, Rangel-Zuñiga OA, Clemente-Postigo M, Podadera-Herreros A, Camargo A, Alcalá-Diaz JF, et al. miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset. Mol Ther Nucleic Acids. 2021 Jan 20;23:1035-1052
NO The authors are grateful to the Andalusian Bioinformatics Platform (PAB) Centre located at the University of Málaga (Spain) for the IPA software. We also thank Dr. Gema García (Microscopy, Cytomics and Scientific Imaging Unit of the IMIBIC, Cordoba, Spain) for her help with confocal microscopy studies and Drs. Francisco J. Ro mero Salguero and Irene Humanes-Pérez and Dr. José A. González Reyes for their help with NTA and TEM studies,  respectively. CIBER OBN is an initiative of ISCIII, Spain. This work was supported by Ministerio de Ciencia, Innovación y Universidades/FEDER(BFU2016-76711-R and BFU2017-90578-REDT to M.M.M., AGL2012/39615 to J.L.-M., and AGL2015-67896-P to J.L.-M. and A.C.); Consejería de Salud y Bienestar Social/Junta de Andalucía/FEDER (PI-0159-2016 to R.G.-R. and PI-0092-2017 to M.C.-P.); Plan Propio de Investigación de la Universidad de Córdoba 2019 (Mod 2.5 to R.G.-R.); and Instituto de Salud Carlos III (ISCIII)/ FEDER (PIE14/00005 to J.L.-M. and M.M.M.). M.C.-P. was the recip ient of a postdoctoral grant Juan de la Cierva Formación (FJCI-2017- 32194) from the MICINN (Spain). This study was cofunded by Euro pean Regional Development Fund/European Social Fund “Investingin your future” and Consejería de Economía, Conocimiento, Empresas y Universidad/Junta de Andalucía/FEDER (BIO-0139)
DS RISalud
RD Apr 8, 2025