BBS-Induced Ciliary Defect Enhances Adipogenesis, Causing Paradoxical Higher-Insulin Sensitivity, Glucose Usage, and Decreased Inflammatory Response

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 wou...

Full description

Saved in:
Bibliographic Details
Published in:Cell metabolism 2012-09, Vol.16 (3), p.363-377
Main Authors: Marion, Vincent, Mockel, Anaïs, De Melo, Charlie, Obringer, Cathy, Claussmann, Aurélie, Simon, Alban, Messaddeq, Nadia, Durand, Myriam, Dupuis, Luc, Loeffler, Jean-Philippe, King, Peter, Mutter-Schmidt, Catherine, Petrovsky, Nikolai, Stoetzel, Corinne, Dollfus, Hélène
Format: Article
Language:English
Subjects:
Adipocytes - physiology
Adipogenesis - genetics
Adipogenesis - physiology
Animals
Bardet-Biedl Syndrome - physiopathology
Chaperonins - genetics
Humans
Insulin Resistance - physiology
Mice
Mice, Knockout
Obesity - physiopathology
Signal Transduction - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. ► BBS patients do not present overt inflamed adipose tissue ► BBS12-mediated ciliary defect activates adipogenesis ► BBS12 knockout mouse shows characteristics BBS phenotypes ► Insulin sensitivity correlates with absence of local inflammation in BBS12 mouse
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2012.08.005