title: BBS4 directly affects proliferation and differentiation of adipocytes.
abstract: BBS4 is one of several proteins whose defects cause Bardet-Biedl syndrome (BBS), a multi-systemic disorder, manifesting with marked obesity. BBS4 polymorphisms have been associated with common non-syndromic morbid obesity. BBS4 obesity molecular mechanisms, and the role of the BBS4 gene in adipocyte differentiation and function are not entirely known. We now show that Bbs4 plays a direct and essential role in proliferation and adipogenesis: silencing of Bbs4 in 3T3F442A preadipocytes induced accelerated cell division and aberrant differentiation, evident through morphologic studies (light, scanning and transmission electron microscopy), metabolic analyses (fat accumulation, fatty acid profile and lipolysis) and adipogenic markers transcripts (Cebpα, Pparγ, aP2, ADRP, Perilipin). Throughout adipogenesis and when challenged with fat load, Bbs4 silenced cells accumulate significantly more triglycerides than control adipocytes, albeit in smaller (yet greater in number) droplets containing modified fatty acid profiles. Thus, greater fat accumulation in the silenced cells is a consequence of both a higher rate of adipocyte proliferation and of aberrant differentiation leading to augmented aberrant accumulation of fat per cell. Our findings suggest that the BBS obesity might be partly due to a direct role of BBS4 in physiological and pathophysiological mechanisms that underlie adipose tissue formation relevant to obesity.
authors: National Institute for Biotechnology in the Negev, Ben Gurion University, Beer-Sheva, Israel.
authors: Olga
authors: O
authors: Aksanov
authors: Pnina
authors: P
authors: Green
authors: Ruth Z
authors: RZ
authors: Birk
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015415:Biomarkers; D002455:Cell Division; D005227:Fatty Acids / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: C506281:BBS4 protein, mouse; D015415:Biomarkers; D005227:Fatty Acids; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D014280:Triglycerides