Transcriptional regulation of adipocyte formation by the liver receptor homologue 1 (Lrh1)-Small hetero-dimerization partner (Shp) network.
Altered adipose tissue formation is a well-known effectors of obesity and T2D. Here, we describe the role of Lrh1 and its co-repressor Shp in the control of adipocyte formation. Expression of Lrh1 in the pre-adipocyte containing SVF is induced in obese mice models and humans while Shp expression is reduced. We demonstrate, that Lrh1 is an inhibitor of adipogenesis while Shp acts functions as an activator through repression of Lrh1 activity. This regulation is at least in part modulated by estradiol conversion through the regulation of Cyp19a1 gene expression. In vivo, loss of Lrh1 leads to induced adipogenesis, while loss of Shp causes uncontrolled activation of Lrh1 and reduced adipogenesis. As Shp expression has been linked to the development of obesity and metabolic disorders, it is possible that alterations of the Shp/Lrh1 network lead to changes in adipocyte formation, which might contribute to the development of obesity associated T2D.
Swiss Federal Institute of Technology, ETH Zürich, Competence Centre for Systems Physiology (CC-SPMD), Institute of Food Nutrition and Health, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Nadja
N
Mrosek
Bettina
B
Meissburger
Chikage
C
Mataki
Eva
E
Roeder
Jozef
J
Ukropec
Iwar
I
Klimes
Daniela
D
Gasperikova
Peter-Paul
PP
Nawroth
Gottfried
G
Rudofsky
Johan
J
Auwerx
Kristina
K
Schoonjans
Christian
C
Wolfrum
Adipocyte; Adipogenesis; Diabetes; Obesity