TY - JOUR
T1 - A microRNA Cluster Controls Fat Cell Differentiation and Adipose Tissue Expansion By Regulating SNCG
AU - Rodríguez-Barrueco, Ruth
AU - Latorre, Jessica
AU - Devis-Jáuregui, Laura
AU - Lluch, Aina
AU - Bonifaci, Nuria
AU - Llobet, Francisco J.
AU - Olivan, Mireia
AU - Coll-Iglesias, Laura
AU - Gassner, Katja
AU - Davis, Meredith L.
AU - Moreno-Navarrete, José M.
AU - Castells-Nobau, Anna
AU - Plata-Peña, Laura
AU - Dalmau-Pastor, Miki
AU - Höring, Marcus
AU - Liebisch, Gerhard
AU - Olkkonen, Vesa M.
AU - Arnoriaga-Rodríguez, Maria
AU - Ricart, Wifredo
AU - Fernández-Real, José M.
AU - Silva, José M.
AU - Ortega, Francisco J.
AU - Llobet-Navas, David
N1 - Funding Information:
The authors are indebted to the participants of the FATBANK platform, promoted by the CIBEROBN and the IDIBGI Biobank (Biobanc IDIBGI, B.0000872), and integrated in the Spanish National Biobanks Network, for their collaboration and coordination. The authors thank the IMIM Microarray Analysis Service (Hospital del Mar Medical Research Institute; Barcelona, Spain) for technical assistance. This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects CP17/00063, CP19/00109, and PI18/00550 (Cofounded by European Regional Development Fund (ERDF) “a way to build Europe,” by the European Social Fund (ESF), “investing in your future”), by the grant RTI2018‐095611‐A‐I00 funded by MCIN/AEI/10.13039/501100011033 and the European Union, and by the Marató de TV3 Foundation (Project #201623‐30‐31). The authors also want to thank the CERCA and PERIS programmes (Generalitat de Catalunya) for financial support. R.R.‐B. (RyC‐2016‐19671) is recipient of a Ramón y Cajal scheme, and D.L.‐N. (MS17/00063) and F.J.O. (MS19/00109) are recipients of a Miguel Servet scheme; Ministerio de Ciencia, Innovación y Universidades, Gobierno de España (ES).
Funding Information:
The authors are indebted to the participants of the FATBANK platform, promoted by the CIBEROBN and the IDIBGI Biobank (Biobanc IDIBGI, B.0000872), and integrated in the Spanish National Biobanks Network, for their collaboration and coordination. The authors thank the IMIM Microarray Analysis Service (Hospital del Mar Medical Research Institute; Barcelona, Spain) for technical assistance. This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects CP17/00063, CP19/00109, and PI18/00550 (Cofounded by European Regional Development Fund (ERDF) ?a way to build Europe,? by the European Social Fund (ESF), ?investing in your future?), by the grant RTI2018-095611-A-I00 funded by MCIN/AEI/10.13039/501100011033 and the European Union, and by the Marat? de TV3 Foundation (Project #201623-30-31). The authors also want to thank the CERCA and PERIS programmes (Generalitat de Catalunya) for financial support. R.R.-B. (RyC-2016-19671) is recipient of a Ram?n y Cajal scheme, and D.L.-N. (MS17/00063) and F.J.O. (MS19/00109) are recipients of a Miguel Servet scheme; Ministerio de Ciencia, Innovaci?n y Universidades, Gobierno de Espa?a (ES).
Publisher Copyright:
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH
PY - 2022/2/2
Y1 - 2022/2/2
N2 - The H19X-encoded miR-424(322)/503 cluster regulates multiple cellular functions. Here, it is reported for the first time that it is also a critical linchpin of fat mass expansion. Deletion of this miRNA cluster in mice results in obesity, while increasing the pool of early adipocyte progenitors and hypertrophied adipocytes. Complementary loss and gain of function experiments and RNA sequencing demonstrate that miR-424(322)/503 regulates a conserved genetic program involved in the differentiation and commitment of white adipocytes. Mechanistically, it is demonstrated that miR-424(322)/503 targets γ-Synuclein (SNCG), a factor that mediates this program rearrangement by controlling metabolic functions in fat cells, allowing adipocyte differentiation and adipose tissue enlargement. Accordingly, diminished miR-424(322) in mice and obese humans co-segregate with increased SNCG in fat and peripheral blood as mutually exclusive features of obesity, being normalized upon weight loss. The data unveil a previously unknown regulatory mechanism of fat mass expansion tightly controlled by the miR-424(322)/503 through SNCG.
AB - The H19X-encoded miR-424(322)/503 cluster regulates multiple cellular functions. Here, it is reported for the first time that it is also a critical linchpin of fat mass expansion. Deletion of this miRNA cluster in mice results in obesity, while increasing the pool of early adipocyte progenitors and hypertrophied adipocytes. Complementary loss and gain of function experiments and RNA sequencing demonstrate that miR-424(322)/503 regulates a conserved genetic program involved in the differentiation and commitment of white adipocytes. Mechanistically, it is demonstrated that miR-424(322)/503 targets γ-Synuclein (SNCG), a factor that mediates this program rearrangement by controlling metabolic functions in fat cells, allowing adipocyte differentiation and adipose tissue enlargement. Accordingly, diminished miR-424(322) in mice and obese humans co-segregate with increased SNCG in fat and peripheral blood as mutually exclusive features of obesity, being normalized upon weight loss. The data unveil a previously unknown regulatory mechanism of fat mass expansion tightly controlled by the miR-424(322)/503 through SNCG.
UR - http://www.scopus.com/inward/record.url?scp=85120976849&partnerID=8YFLogxK
U2 - 10.1002/advs.202104759
DO - 10.1002/advs.202104759
M3 - Article
C2 - 34898027
AN - SCOPUS:85120976849
SN - 2198-3844
VL - 9
JO - Advanced Science
JF - Advanced Science
IS - 4
M1 - 2104759
ER -