Advanced Science (Feb 2022)
A microRNA Cluster Controls Fat Cell Differentiation and Adipose Tissue Expansion By Regulating SNCG
- 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
Affiliations
- Ruth Rodríguez‐Barrueco
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- Jessica Latorre
- Department of Diabetes Endocrinology, and Nutrition (UDEN) Institut d'Investigació Biomèdica de Girona (IDIBGI) Salt 17190 Spain
- Laura Devis‐Jáuregui
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- Aina Lluch
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- Nuria Bonifaci
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- Francisco J. Llobet
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- Mireia Olivan
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- Laura Coll‐Iglesias
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- Katja Gassner
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- Meredith L. Davis
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- José M. Moreno‐Navarrete
- Department of Diabetes Endocrinology, and Nutrition (UDEN) Institut d'Investigació Biomèdica de Girona (IDIBGI) Salt 17190 Spain
- Anna Castells‐Nobau
- Department of Diabetes Endocrinology, and Nutrition (UDEN) Institut d'Investigació Biomèdica de Girona (IDIBGI) Salt 17190 Spain
- Laura Plata‐Peña
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- Miki Dalmau‐Pastor
- Anatomy Unit Department of Pathology and Experimental Therapy School of Medicine University of Barcelona (UB) L'Hospitalet de Llobregat 08907 Spain
- Marcus Höring
- Institute of Clinical Chemistry and Laboratory Medicine Regensburg University Hospital Regensburg 93053 Germany
- Gerhard Liebisch
- Institute of Clinical Chemistry and Laboratory Medicine Regensburg University Hospital Regensburg 93053 Germany
- Vesa M. Olkkonen
- Minerva Foundation Institute for Medical Research (Biomedicum 2U) and Department of Anatomy Faculty of Medicine University of Helsinki Helsinki 00290 Finland
- Maria Arnoriaga‐Rodríguez
- Department of Diabetes Endocrinology, and Nutrition (UDEN) Institut d'Investigació Biomèdica de Girona (IDIBGI) Salt 17190 Spain
- Wifredo Ricart
- Department of Diabetes Endocrinology, and Nutrition (UDEN) Institut d'Investigació Biomèdica de Girona (IDIBGI) Salt 17190 Spain
- José M. Fernández‐Real
- Department of Diabetes Endocrinology, and Nutrition (UDEN) Institut d'Investigació Biomèdica de Girona (IDIBGI) Salt 17190 Spain
- José M. Silva
- Department of Pathology Icahn School of Medicine at Mount Sinai New York NY 10029 USA
- Francisco J. Ortega
- Department of Diabetes Endocrinology, and Nutrition (UDEN) Institut d'Investigació Biomèdica de Girona (IDIBGI) Salt 17190 Spain
- David Llobet‐Navas
- Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat 08908 Spain
- DOI
- https://doi.org/10.1002/advs.202104759
- Journal volume & issue
-
Vol. 9,
no. 4
pp. n/a – n/a
Abstract
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.
Keywords
