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

Rodriguez-Barrueco, Ruth and Latorre, Jessica and Devis-Jauregui, Laura and Lluch, Aina and Bonifaci, Nuria and Llobet, Francisco J. and Olivan, Mireia and Coll-Iglesias, Laura and Gassner, Katja and Davis, Meredith L. and Moreno-Navarrete, Jose M. and Castells-Nobau, Anna and Plata-Pena, Laura and Dalmau-Pastor, Miki and Höring, Marcus and Liebisch, Gerhard and Olkkonen, Vesa M. and Arnoriaga-Rodriguez, Maria and Ricart, Wifredo and Fernandez-Real, Jose M. and Silva, Jose M. and Ortega, Francisco J. and Llobet-Navas, David (2022) A microRNA Cluster Controls Fat Cell Differentiation and Adipose Tissue Expansion By Regulating SNCG. ADVANCED SCIENCE, 9 (4): 2104759. ISSN 2198-3844

Full text not available from this repository. (Request a copy)

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 gamma-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 offat mass expansion tightly controlled by the miR-424(322)/503 through SNCG.

Item Type: Article
Uncontrolled Keywords: TANDEM MASS-SPECTROMETRY; GROWTH-FACTOR-BETA; HIGH-THROUGHPUT QUANTIFICATION; ADIPOCYTE PRECURSOR CELLS; SET ENRICHMENT ANALYSIS; BREAST-CANCER CELLS; TRANSCRIPTION FACTORS; INSULIN SENSITIVITY; EXPRESSION ANALYSIS; LIPID EXTRACTION; gamma-Synuclein; adipocytes; adipose tissue; miR-424(322)/503; obesity
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Sep 2022 04:17
Last Modified: 14 Sep 2022 04:17
URI: https://pred.uni-regensburg.de/id/eprint/48101

Actions (login required)

View Item View Item