A microRNA Cluster Controls Fat Cell Differentiation and Adipose Tissue Expansion By Regulating SNCG

Abstract: 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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
A microRNA Cluster Controls Fat Cell Differentiation and Adipose Tissue Expansion By Regulating SNCG ; day:13 ; month:12 ; year:2021 ; extent:22
Advanced science ; (13.12.2021) (gesamt 22)

Urheber
Rodríguez‐Barrueco, Ruth
Latorre, Jessica
Devis‐Jáuregui, Laura
Lluch, Aina
Bonifaci, Nuria
Llobet, Francisco J.
Olivan, Mireia
Coll‐Iglesias, Laura
Gassner, Katja
Davis, Meredith L.
Moreno‐Navarrete, José M.
Castells‐Nobau, Anna
Plata‐Peña, Laura
Dalmau‐Pastor, Miki
Höring, Marcus
Liebisch, Gerhard
Olkkonen, Vesa M.
Arnoriaga‐Rodríguez, Maria
Ricart, Wifredo
Fernández‐Real, José M.
Silva, José M.
Ortega, Francisco J.
Llobet‐Navas, David

DOI
10.1002/advs.202104759
URN
urn:nbn:de:101:1-2021121314063737092750
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
2025-08-15T07:35:24+0200

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Beteiligte

  • Rodríguez‐Barrueco, Ruth
  • Latorre, Jessica
  • Devis‐Jáuregui, Laura
  • Lluch, Aina
  • Bonifaci, Nuria
  • Llobet, Francisco J.
  • Olivan, Mireia
  • Coll‐Iglesias, Laura
  • Gassner, Katja
  • Davis, Meredith L.
  • Moreno‐Navarrete, José M.
  • Castells‐Nobau, Anna
  • Plata‐Peña, Laura
  • Dalmau‐Pastor, Miki
  • Höring, Marcus
  • Liebisch, Gerhard
  • Olkkonen, Vesa M.
  • Arnoriaga‐Rodríguez, Maria
  • Ricart, Wifredo
  • Fernández‐Real, José M.
  • Silva, José M.
  • Ortega, Francisco J.
  • Llobet‐Navas, David

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