Hallenborg, Philip, Jensen, Benjamin Anderschou Holbech, Fjaere, Even, Petersen, Rasmus Koefoed, Belmaati, Mohammed-Samir, Rasmussen, Sarah Sondergard, Gunnarsson, Jon Petur, Lauritzen, Pernille, Cheng, Kenneth King Yip, Hermansson, Martin, Sonne, Si Brask, Ejsing, Christer S. ORCID: 0000-0003-4963-0276, Xu, Aimin, Kratchmarova, Irina, Krueger, Marcus, Madsen, Lise, Kristiansen, Karsten and Blagoev, Blagoy ORCID: 0000-0002-3596-0066 (2021). Adipose MDM2 regulates systemic insulin sensitivity. Sci Rep, 11 (1). BERLIN: NATURE PORTFOLIO. ISSN 2045-2322

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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 PPAR gamma coactivation. Collectively, these data argue for a hitherto unknown interplay between MDM2 and MORC2/LIPIN1 involved in balancing adipocyte function.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hallenborg, PhilipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jensen, Benjamin Anderschou HolbechUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fjaere, EvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petersen, Rasmus KoefoedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belmaati, Mohammed-SamirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rasmussen, Sarah SondergardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gunnarsson, Jon PeturUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lauritzen, PernilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cheng, Kenneth King YipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hermansson, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sonne, Si BraskUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ejsing, Christer S.UNSPECIFIEDorcid.org/0000-0003-4963-0276UNSPECIFIED
Xu, AiminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kratchmarova, IrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madsen, LiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kristiansen, KarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blagoev, BlagoyUNSPECIFIEDorcid.org/0000-0002-3596-0066UNSPECIFIED
URN: urn:nbn:de:hbz:38-597883
DOI: 10.1038/s41598-021-01240-3
Journal or Publication Title: Sci Rep
Volume: 11
Number: 1
Date: 2021
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACTIVATED RECEPTOR-GAMMA; RESTING METABOLIC-RATE; PPAR-GAMMA; ENERGY-EXPENDITURE; TUMOR-SUPPRESSOR; FAMILY PROTEINS; AMINO-ACIDS; P53; EXPRESSION; MOUSEMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59788

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