A microRNA cluster controls fat cell differentiation and adipose tissue expansion by regulating SNCG
| Autor: | Ruth Rodríguez‐Barrueco, Jessica Latorre, Laura Devis‐Jáuregui, Aina Lluch, Nuria Bonifaci, Francisco J. Llobet, Mireia Olivan, Laura Coll‐Iglesias, Katja Gassner, Meredith L. Davis, José M. Moreno‐Navarrete, Anna Castells‐Nobau, Laura Plata‐Peña, Miki Dalmau‐Pastor, Marcus Höring, Gerhard Liebisch, Vesa M. Olkkonen, Maria Arnoriaga‐Rodríguez, Wifredo Ricart, José M. Fernández‐Real, José M. Silva, Francisco J. Ortega, David Llobet‐Navas |
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| Přispěvatelé: | Medicum, Department of Anatomy |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
miR‐424(322)/503 obesity γ‐Synuclein General Chemical Engineering adipocytes Science General Physics and Astronomy Medicine (miscellaneous) ADIPOCYTE PRECURSOR CELLS Biochemistry Genetics and Molecular Biology (miscellaneous) Mice gamma-Synuclein Cell diferentiation Animals Humans General Materials Science Obesity TANDEM MASS-SPECTROMETRY Experimentació animal LIPID EXTRACTION Mice Inbred BALB C Adipogenesis GROWTH-FACTOR-BETA INSULIN SENSITIVITY SET ENRICHMENT ANALYSIS General Engineering BREAST-CANCER CELLS Cell Differentiation Adipose tissues miR-424(322)/503 HIGH-THROUGHPUT QUANTIFICATION Neoplasm Proteins adipose tissue Mice Inbred C57BL TRANSCRIPTION FACTORS MicroRNAs Teixit adipós 3121 General medicine internal medicine and other clinical medicine Animal experimentation 1182 Biochemistry cell and molecular biology Obesitat Female 3111 Biomedicine Diferenciació cel·lular EXPRESSION ANALYSIS |
| Zdroj: | Advanced Science, Vol 9, Iss 4, Pp n/a-n/a (2022) Dipòsit Digital de la UB Universidad de Barcelona |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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