title: 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.
authors.affiliation: Laboratoire de Physiopathologie des Syndromes Rares Héréditaires, AVENIR-Inserm, EA3949, Université de Strasbourg, 11 rue Humann, 67085 Strasbourg, France. vincent.marion@unistra.fr
authors.forename: Vincent
authors.initials: V
authors.lastname: Marion
authors.forename: Anaïs
authors.initials: A
authors.lastname: Mockel
authors.forename: Charlie
authors.initials: C
authors.lastname: De Melo
authors.forename: Cathy
authors.initials: C
authors.lastname: Obringer
authors.forename: Aurélie
authors.initials: A
authors.lastname: Claussmann
authors.forename: Alban
authors.initials: A
authors.lastname: Simon
authors.forename: Nadia
authors.initials: N
authors.lastname: Messaddeq
authors.forename: Myriam
authors.initials: M
authors.lastname: Durand
authors.forename: Luc
authors.initials: L
authors.lastname: Dupuis
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Loeffler
authors.forename: Peter
authors.initials: P
authors.lastname: King
authors.forename: Catherine
authors.initials: C
authors.lastname: Mutter-Schmidt
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
authors.forename: Corinne
authors.initials: C
authors.lastname: Stoetzel
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000503:physiopathology*; D018833:Chaperonins / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C547664:Bbs12 protein, mouse; D018833:Chaperonins