title: Insulin regulates Bbs4 during adipogenesis.
abstract: Bardet-Biedl syndrome (BBS) is a pleiotropic autosomal recessive disorder associated with marked obesity, increased susceptibility to insulin resistance and type 2 diabetes. However, it is unknown whether the link between BBS and diabetes is indirect or direct. Adipogenesis and adipocyte function are regulated by hormonal stimuli, with insulin and insulin growth factor (IGF) playing an important role both in normal and impaired conditions. We have previously shown augmented transcript levels of BBS genes upon induction of adipogenesis. The aim of this study was to investigate the role of insulin in BBS. Through in vitro studies in adipocytes in which Bbs4 expression was either silenced (SiBbs4) or overexpressed (OEBbs4), we showed that insulin and IGF dose- and time-dependently decrease transcription and protein expression of BBS genes during adipogenesis. Silencing of Bbs4 expression in adipocytes significantly impaired and reduced glucose uptake. This effect was reversed by Bbs4 overexpression. Inhibition of PI 3-kinase resulted in upregulation of Bbs transcripts, suggesting that the PI3K pathway is involved in the regulation of these genes. In conclusion, we showed that insulin is a direct regulator of Bbs1, 2, 4 and 6. This hormonal regulation might indicate a metabolic link of these genes to obesity and metabolic syndrome. © 2017 IUBMB Life, 69(7):489-499, 2017.
authors.affiliation: Department of Biotechnology and Epidemiology, Ben-Gurion University, Beer-Sheva, Israel.|Department of Nutrition, School of Health Science, Ariel University, Ariel, Israel.
authors.forename: Netta
authors.initials: N
authors.lastname: Nahum
authors.affiliation: Department of Biotechnology and Epidemiology, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Forti
authors.affiliation: Department of Biotechnology and Epidemiology, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Aksanov
authors.affiliation: Department of Nutrition, School of Health Science, Ariel University, Ariel, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Birk
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011506:Proteins / Q000235:genetics
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D005947:Glucose; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011506:Proteins; C506281:BBS4 protein, mouse; C506280:Bbs1 protein, mouse; C528012:Bbs2 protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: Bardet-Biedl syndrome; IGF; adipogenesis; insulin