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BBS-induced ciliary defect enhances adipogenesis, causing paradoxical higher-insulin sensitivity, glucose usage, and decreased inflammatory response.

BBS-induced ciliary defect enhances adipogenesis, causing paradoxical higher-insulin sensitivity, glucose usage, and decreased inflammatory response.

Authors :
Marion V
Mockel A
De Melo C
Obringer C
Claussmann A
Simon A
Messaddeq N
Durand M
Dupuis L
Loeffler JP
King P
Mutter-Schmidt C
Petrovsky N
Stoetzel C
Dollfus H
Source :
Cell metabolism [Cell Metab] 2012 Sep 05; Vol. 16 (3), pp. 363-77.
Publication Year :
2012

Abstract

Studying ciliopathies, like the Bardet-Biedl syndrome (BBS), allow the identification of signaling pathways potentially involved in common diseases, sharing phenotypic features like obesity or type 2 diabetes. Given the close association between obesity and insulin resistance, obese BBS patients would be expected to be insulin resistant. Surprisingly, we found that a majority of obese BBS patients retained normal glucose tolerance and insulin sensitivity. Patient's adipose tissue biopsies revealed upregulation of adipogenic genes and decrease of inflammatory mediators. In vitro studies on human primary mesenchymal stem cells (MSCs) showed that BBS12 inactivation facilitated adipogenesis, increased insulin sensitivity, and glucose utilization. We generated a Bbs12(-/-) mouse model to assess the impact of Bbs12 inactivation on adipocyte biology. Despite increased obesity, glucose tolerance was increased with specific enhanced insulin sensitivity in the fat. This correlated with an active recruitment of MSCs resulting in adipose tissue hyperplasia and decreased in inflammation.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1932-7420
Volume :
16
Issue :
3
Database :
MEDLINE
Journal :
Cell metabolism
Publication Type :
Academic Journal
Accession number :
22958920
Full Text :
https://doi.org/10.1016/j.cmet.2012.08.005