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@ARTICLE{BayindirBuchhalter:136847,
author = {I. Bayindir-Buchhalter and G. Wolff$^*$ and S. Lerch$^*$
and T. Sijmonsma$^*$ and M. Schuster$^*$ and J. Gronych$^*$
and A. T. Billeter and R. Babaei$^*$ and D. Krunic$^*$ and
L. Ketscher and N. Spielmann and M. Hrabe de Angelis and J.
L. Ruas and B. P. Müller-Stich and M. Heikenwalder$^*$ and
P. Lichter$^*$ and S. Herzig and A. Vegiopoulos$^*$},
title = {{C}ited4 is a sex-biased mediator of the antidiabetic
glitazone response in adipocyte progenitors.},
journal = {EMBO molecular medicine},
volume = {10},
number = {8},
issn = {1757-4684},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {DKFZ-2018-01285},
pages = {e8613},
year = {2018},
abstract = {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.},
cin = {A171 / F180 / B060 / L101 / W210},
ddc = {610},
cid = {I:(DE-He78)A171-20160331 / I:(DE-He78)F180-20160331 /
I:(DE-He78)B060-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)W210-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29973382},
pmc = {pmc:PMC6079535},
doi = {10.15252/emmm.201708613},
url = {https://inrepo02.dkfz.de/record/136847},
}