TY - JOUR
T1 - Investigating the involvement of the ATF6α pathway of the unfolded protein response in adipogenesis
AU - Lowe, C E
AU - Dennis, R J
AU - Obi, U
AU - O'Rahilly, S
AU - Rochford, J J
PY - 2012/9/1
Y1 - 2012/9/1
N2 - 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.
AB - 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.
KW - adipogenesis
KW - unfolded protein response
KW - ATF6a
UR - http://www.scopus.com/inward/record.url?scp=84866350594&partnerID=8YFLogxK
U2 - 10.1038/ijo.2011.233
DO - 10.1038/ijo.2011.233
M3 - Article
AN - SCOPUS:84866350594
SN - 0307-0565
VL - 36
SP - 1248
EP - 1251
JO - International Journal of Obesity
JF - International Journal of Obesity
ER -