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

Vincent Marion, Anais Mockel, Charlie De Melo, Cathy Obringer, Aurelie Claussmann, Alban Simon, Nadia Massaddeq, Myriam Durand, Luc Dupuis, Jean-Phillippe Loeffler, Peter King, Catherine Mutter-Schmidt, Nikolai Petrovsky, Corinne Stoetzel, Helene Dollfus

    Research output: Contribution to journalArticlepeer-review

    40 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)363-377
    Number of pages15
    JournalCell Metabolism
    Volume16
    Issue number3
    DOIs
    Publication statusPublished - 5 Sep 2012

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