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

Ruth Rodríguez-Barrueco1,2, Jessica Latorre3,4, Laura Devis-Jáuregui1

  • 1Molecular Mechanisms and Experimental Therapy in Oncology-Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 08908, Spain.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|December 13, 2021
PubMed
Summary

The miR-424(322)/503 microRNA cluster is crucial for controlling fat mass. Its absence causes obesity by promoting adipocyte development, highlighting a new mechanism involving SNCG.

Keywords:
adipocytesadipose tissuemiR-424(322)/503obesityγ-Synuclein

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Area of Science:

  • Molecular Biology
  • Genetics
  • Metabolic Research

Background:

  • The H19X-encoded miR-424(322)/503 microRNA cluster is known to regulate various cellular functions.
  • The precise role of this miRNA cluster in metabolic regulation, particularly in fat mass expansion, remains largely unexplored.

Purpose of the Study:

  • To investigate the role of the miR-424(322)/503 cluster in the regulation of fat mass expansion.
  • To elucidate the molecular mechanisms underlying the cluster's function in adipocyte differentiation and adipose tissue development.

Main Methods:

  • Utilized genetically modified mice with deletion of the miR-424(322)/503 miRNA cluster.
  • Performed loss-of-function and gain-of-function experiments.
  • Conducted RNA sequencing to analyze gene expression changes.
  • Investigated the interaction between miR-424(322)/503 and its target gene, γ-Synuclein (SNCG).

Main Results:

  • Deletion of the miR-424(322)/503 cluster in mice led to obesity, characterized by an increased pool of adipocyte progenitors and hypertrophied adipocytes.
  • miR-424(322)/503 was found to regulate a conserved genetic program essential for white adipocyte differentiation and commitment.
  • Mechanistically, miR-424(322)/503 targets SNCG, which mediates metabolic functions crucial for adipocyte differentiation and adipose tissue expansion.
  • Diminished miR-424(322) levels and increased SNCG expression were observed in both obese mice and humans, with levels normalizing upon weight loss.

Conclusions:

  • The miR-424(322)/503 microRNA cluster is a critical regulator of fat mass expansion.
  • The cluster exerts its function by targeting SNCG, thereby controlling adipocyte differentiation and adipose tissue growth.
  • This study reveals a novel regulatory pathway for obesity involving the miR-424(322)/503-SNCG axis.