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Bayindir-Buchhalter, I.* ; Wolff, G.* ; Lerch, S.* ; Sijmonsma, T.* ; Schuster, M.* ; Gronych, J.* ; Billeter, A.T.* ; Babaei, R.* ; Krunic, D.* ; Ketscher, L.* ; Spielmann, N. ; Hrabě de Angelis, M. ; Ruas, J.L.* ; Müller-Stich, B.P.* ; Heikenwalder, M.* ; Lichter, P.* ; Herzig, S. ; Vegiopoulos, A.*

Cited4 is a sex-biased mediator of the antidiabetic glitazone response in adipocyte progenitors.

EMBO Mol. Med. 10:e8613 (2018)
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Most antidiabetic drugs treat disease symptoms rather than adipose tissue dysfunction as a key pathogenic cause in the metabolic syndrome and type 2 diabetes. Pharmacological targeting of adipose tissue through the nuclear receptor PPARg, as exemplified by glitazone treatments, mediates efficacious insulin sensitization. However, a better understanding of the context-specific PPARg responses is required for the development of novel approaches with reduced side effects. Here, we identified the transcriptional cofactor Cited4 as a target and mediator of rosiglitazone in human and murine adipocyte progenitor cells, where it promoted specific sets of the rosiglitazone-dependent transcriptional program. In mice, Cited4 was required for the proper induction of thermogenic expression by Rosi specifically in subcutaneous fat. This phenotype had high penetrance in females only and was not evident in beta-adrenergically stimulated browning. Intriguingly, this specific defect was associated with reduced capacity for systemic thermogenesis and compromised insulin sensitization upon therapeutic rosiglitazone treatment in female but not male mice. Our findings on Cited4 function reveal novel unexpected aspects of the pharmacological targeting of PPARg.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adipocyte Progenitors ; Browning ; Cited4 ; Glitazones ; Insulin Sensitivity; Activated Receptor-gamma; White Adipose-tissue; Ppar-gamma; Insulin-resistance; Skeletal-muscle; Rosiglitazone Treatment; Mitochondrial Biogenesis; Uncoupling Protein-1; Diabetic-patients; Brown Adipocytes
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 1757-4676
e-ISSN 1757-4684
Journal EMBO Molecular Medicine
Quellenangaben Volume: 10, Issue: 7, Pages: , Article Number: e8613 Supplement: ,
Publisher Wiley
Publishing Place Chichester
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Diabetes and Cancer (IDC)
POF-Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
Research field(s) Genetics and Epidemiology
Helmholtz Diabetes Center
PSP Element(s) G-500600-001
G-500692-001
G-501900-251
DOI 10.15252/emmm.201708613
WOS ID WOS:000440915000003
Scopus ID 85050452184
PubMed ID 29973382
Erfassungsdatum 2018-07-11
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