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

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

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 eff...

Full description

Saved in:
Bibliographic Details
Main Authors: Irem Bayindir‐Buchhalter, Gretchen Wolff, Sarah Lerch, Tjeerd Sijmonsma, Maximilian Schuster, Jan Gronych, Adrian T Billeter, Rohollah Babaei, Damir Krunic, Lars Ketscher, Nadine Spielmann, Martin Hrabe de Angelis, Jorge L Ruas, Beat P Müller‐Stich, Mathias Heikenwalder, Peter Lichter, Stephan Herzig, Alexandros Vegiopoulos
Format: Article
Language:English
Published: Springer Nature 2018-07-01
Series:EMBO Molecular Medicine
Subjects:
adipocyte progenitors
browning
Cited4
glitazones
insulin sensitivity
Online Access:https://doi.org/10.15252/emmm.201708613
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1757-4676
1757-4684

Similar Items