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

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.

journal_name

Cell Metab

journal_title

Cell metabolism

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

doi

10.1016/j.cmet.2012.08.005

subject

Has Abstract

pub_date

2012-09-05 00:00:00

pages

363-77

issue

3

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(12)00327-0

journal_volume

16

pub_type

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