BBS-Induced Ciliary Defect Enhances Adipogenesis, Causing Paradoxical Higher-Insulin Sensitivity, Glucose Usage, and Decreased Inflammatory Response
| Autor: | Luc Dupuis, Myriam Durand, Vincent Marion, Jean-Philippe Loeffler, Charlie De Melo, Alban Simon, Peter J. King, Aurélie Claussmann, Nikolai Petrovsky, Hélène Dollfus, Cathy Obringer, Catherine Mutter-Schmidt, Nadia Messaddeq, Anais Mockel, Corinne Stoetzel |
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| Rok vydání: | 2012 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities medicine.medical_specialty Chaperonins Physiology Adipose tissue Inflammation Type 2 diabetes Biology Mice chemistry.chemical_compound Insulin resistance Downregulation and upregulation Adipocyte Internal medicine Adipocytes medicine Animals Humans Obesity Bardet-Biedl Syndrome Molecular Biology Mice Knockout Adipogenesis Mesenchymal stem cell Cell Biology medicine.disease Endocrinology chemistry Insulin Resistance medicine.symptom Signal Transduction |
| Zdroj: | Cell Metabolism. 16:363-377 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2012.08.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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