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 - 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 -