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000136847 1001_ $$0P:(DE-He78)403b3fa7b66eb16193fff3acddeddcbd$$aBayindir-Buchhalter, Irem$$b0$$eFirst author
000136847 245__ $$aCited4 is a sex-biased mediator of the antidiabetic glitazone response in adipocyte progenitors.
000136847 260__ $$aWeinheim$$bWiley-VCH$$c2018
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000136847 520__ $$aMost antidiabetic drugs treat disease symptoms rather than adipose tissue dysfunction as a key pathogenic cause in the metabolic syndrome and type 2 diabetes. Pharmacological targeting of adipose tissue through the nuclear receptor PPARg, as exemplified by glitazone treatments, mediates efficacious insulin sensitization. However, a better understanding of the context-specific PPARg responses is required for the development of novel approaches with reduced side effects. Here, we identified the transcriptional cofactor Cited4 as a target and mediator of rosiglitazone in human and murine adipocyte progenitor cells, where it promoted specific sets of the rosiglitazone-dependent transcriptional program. In mice, Cited4 was required for the proper induction of thermogenic expression by Rosi specifically in subcutaneous fat. This phenotype had high penetrance in females only and was not evident in beta-adrenergically stimulated browning. Intriguingly, this specific defect was associated with reduced capacity for systemic thermogenesis and compromised insulin sensitization upon therapeutic rosiglitazone treatment in female but not male mice. Our findings on Cited4 function reveal novel unexpected aspects of the pharmacological targeting of PPARg.
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000136847 7001_ $$0P:(DE-He78)f84dcecd50e74fd7f6e5cf21e876e49c$$aWolff, Gretchen$$b1
000136847 7001_ $$0P:(DE-He78)8f17e5ade9bb27444b5e417a0bd1c115$$aLerch, Sarah$$b2
000136847 7001_ $$0P:(DE-He78)2907fb4a25af2d45366a9dbc819ca116$$aSijmonsma, Tjeerd$$b3
000136847 7001_ $$0P:(DE-He78)e4e46a1b1ab86b4e42749dc3a565983d$$aSchuster, Maximilian$$b4
000136847 7001_ $$0P:(DE-He78)bb186a8b38fef24ebd6f11918ade985d$$aGronych, Jan$$b5
000136847 7001_ $$aBilleter, Adrian T$$b6
000136847 7001_ $$0P:(DE-He78)8490712a5ba120ddbe28b80e1b3f436a$$aBabaei, Rohollah$$b7
000136847 7001_ $$0P:(DE-He78)2214defe87d04a849413e5eed47c415e$$aKrunic, Damir$$b8
000136847 7001_ $$aKetscher, Lars$$b9
000136847 7001_ $$aSpielmann, Nadine$$b10
000136847 7001_ $$aHrabe de Angelis, Martin$$b11
000136847 7001_ $$00000-0002-1110-2606$$aRuas, Jorge L$$b12
000136847 7001_ $$aMüller-Stich, Beat P$$b13
000136847 7001_ $$0P:(DE-He78)66ed2d4ec9bc11d29b87ac006adf85e5$$aHeikenwalder, Mathias$$b14
000136847 7001_ $$0P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c$$aLichter, Peter$$b15
000136847 7001_ $$aHerzig, Stephan$$b16
000136847 7001_ $$0P:(DE-He78)4870f7888cc3a0e026e08d4188a9fd48$$aVegiopoulos, Alexandros$$b17$$eLast author
000136847 773__ $$0PERI:(DE-600)2485479-7$$a10.15252/emmm.201708613$$gVol. 10, no. 8, p. e8613 -$$n8$$pe8613$$tEMBO molecular medicine$$v10$$x1757-4684$$y2018
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