title: Investigating the involvement of the ATF6α pathway of the unfolded protein response in adipogenesis.
abstract: The unfolded protein response (UPR) is activated by endoplasmic reticulum stress resulting from an accumulation of unfolded or mis-folded proteins. The UPR is divided into three arms, involving the activation of ATF-6, PERK and IRE-1, that together act to restrict new protein synthesis and increase the production of chaperones. Recent studies have implicated the PERK and IRE-1 components of the UPR in adipocyte differentiation. In this study, we investigate the importance of ATF6α during adipogenesis using stable knockdown of this protein in the model adipogenic cell line, C3H10T1/2. Reduction of ATF6α expression by >70% resulted in impaired expression of key adipogenic genes and reduced lipid accumulation following the induction of adipogenesis. In contrast, loss of ATF6α did not impair the ability of cells to undergo osteogenic differentiation. Overall, our data indicate that all three arms of the UPR, including ATF6α, must be intact to permit adipogenesis to occur.
authors: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
authors: C E
authors: CE
authors: Lowe
authors: R J
authors: RJ
authors: Dennis
authors: U
authors: U
authors: Obi
authors: S
authors: S
authors: O'Rahilly
authors: J J
authors: JJ
authors: Rochford
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D056811:Unfolded Protein Response / Q000235:genetics; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; C497112:Atf6 protein, mouse; C486556:Ern2 protein, mouse