Adipose MDM2 regulates systemic insulin sensitivity

Abstract The intimate association between obesity and type II diabetes urges for a deeper understanding of adipocyte function. We and others have previously delineated a role for the tumor suppressor p53 in adipocyte biology. Here, we show that mice haploinsufficient for MDM2, a key regulator of p53...

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Autores principales:	Philip Hallenborg, Benjamin Anderschou Holbech Jensen, Even Fjære, Rasmus Koefoed Petersen, Mohammed-Samir Belmaâti, Sarah Søndergård Rasmussen, Jon Petur Gunnarsson, Pernille Lauritzen, Kenneth King Yip Cheng, Martin Hermansson, Si Brask Sonne, Christer S. Ejsing, Aimin Xu, Irina Kratchmarova, Marcus Krüger, Lise Madsen, Karsten Kristiansen, Blagoy Blagoev
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/40be2ce071a64faf8d38428ae1f155cb
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spelling	oai:doaj.org-article:40be2ce071a64faf8d38428ae1f155cb2021-11-14T12:20:38ZAdipose MDM2 regulates systemic insulin sensitivity10.1038/s41598-021-01240-32045-2322https://doaj.org/article/40be2ce071a64faf8d38428ae1f155cb2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01240-3https://doaj.org/toc/2045-2322Abstract The intimate association between obesity and type II diabetes urges for a deeper understanding of adipocyte function. We and others have previously delineated a role for the tumor suppressor p53 in adipocyte biology. Here, we show that mice haploinsufficient for MDM2, a key regulator of p53, in their adipose stores suffer from overt obesity, glucose intolerance, and hepatic steatosis. These mice had decreased levels of circulating palmitoleic acid [non-esterified fatty acid (NEFA) 16:1] concomitant with impaired visceral adipose tissue expression of Scd1 and Ffar4. A similar decrease in Scd and Ffar4 expression was found in in vitro differentiated adipocytes with perturbed MDM2 expression. Lowered MDM2 levels led to nuclear exclusion of the transcriptional cofactors, MORC2 and LIPIN1, and thereby possibly hampered adipocyte function by antagonizing LIPIN1-mediated PPARγ coactivation. Collectively, these data argue for a hitherto unknown interplay between MDM2 and MORC2/LIPIN1 involved in balancing adipocyte function.Philip HallenborgBenjamin Anderschou Holbech JensenEven FjæreRasmus Koefoed PetersenMohammed-Samir BelmaâtiSarah Søndergård RasmussenJon Petur GunnarssonPernille LauritzenKenneth King Yip ChengMartin HermanssonSi Brask SonneChrister S. EjsingAimin XuIrina KratchmarovaMarcus KrügerLise MadsenKarsten KristiansenBlagoy BlagoevNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Philip Hallenborg Benjamin Anderschou Holbech Jensen Even Fjære Rasmus Koefoed Petersen Mohammed-Samir Belmaâti Sarah Søndergård Rasmussen Jon Petur Gunnarsson Pernille Lauritzen Kenneth King Yip Cheng Martin Hermansson Si Brask Sonne Christer S. Ejsing Aimin Xu Irina Kratchmarova Marcus Krüger Lise Madsen Karsten Kristiansen Blagoy Blagoev Adipose MDM2 regulates systemic insulin sensitivity
description	Abstract The intimate association between obesity and type II diabetes urges for a deeper understanding of adipocyte function. We and others have previously delineated a role for the tumor suppressor p53 in adipocyte biology. Here, we show that mice haploinsufficient for MDM2, a key regulator of p53, in their adipose stores suffer from overt obesity, glucose intolerance, and hepatic steatosis. These mice had decreased levels of circulating palmitoleic acid [non-esterified fatty acid (NEFA) 16:1] concomitant with impaired visceral adipose tissue expression of Scd1 and Ffar4. A similar decrease in Scd and Ffar4 expression was found in in vitro differentiated adipocytes with perturbed MDM2 expression. Lowered MDM2 levels led to nuclear exclusion of the transcriptional cofactors, MORC2 and LIPIN1, and thereby possibly hampered adipocyte function by antagonizing LIPIN1-mediated PPARγ coactivation. Collectively, these data argue for a hitherto unknown interplay between MDM2 and MORC2/LIPIN1 involved in balancing adipocyte function.
format	article
author	Philip Hallenborg Benjamin Anderschou Holbech Jensen Even Fjære Rasmus Koefoed Petersen Mohammed-Samir Belmaâti Sarah Søndergård Rasmussen Jon Petur Gunnarsson Pernille Lauritzen Kenneth King Yip Cheng Martin Hermansson Si Brask Sonne Christer S. Ejsing Aimin Xu Irina Kratchmarova Marcus Krüger Lise Madsen Karsten Kristiansen Blagoy Blagoev
author_facet	Philip Hallenborg Benjamin Anderschou Holbech Jensen Even Fjære Rasmus Koefoed Petersen Mohammed-Samir Belmaâti Sarah Søndergård Rasmussen Jon Petur Gunnarsson Pernille Lauritzen Kenneth King Yip Cheng Martin Hermansson Si Brask Sonne Christer S. Ejsing Aimin Xu Irina Kratchmarova Marcus Krüger Lise Madsen Karsten Kristiansen Blagoy Blagoev
author_sort	Philip Hallenborg
title	Adipose MDM2 regulates systemic insulin sensitivity
title_short	Adipose MDM2 regulates systemic insulin sensitivity
title_full	Adipose MDM2 regulates systemic insulin sensitivity
title_fullStr	Adipose MDM2 regulates systemic insulin sensitivity
title_full_unstemmed	Adipose MDM2 regulates systemic insulin sensitivity
title_sort	adipose mdm2 regulates systemic insulin sensitivity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/40be2ce071a64faf8d38428ae1f155cb
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Adipose MDM2 regulates systemic insulin sensitivity

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