Characterization of Tunicamycin as Anti-obesity Agent

Adipocytes undergo adipocyte stress in the excessive presence of lipid. Adipocyte stress accompanies the typical signs of endoplasmic reticulum (ER) stress: unfolded protein response and overexpression of molecular chaperones. Apoptotic induction in adipocytes is known as a good strategy for treating obesity. The drug "tunicamycin" was tested for its therapeutic potential in inducing apoptosis on differentiating adipocytes of 3T3-L1. When the 3T3-L1 cells, stimulated for adipogenesis, were treated with tunicamycin, they showed typical ER stress symptoms. Despite progression in ER stress, however, the differentiated 3T3-L1 hardly proceeded to apoptosis based on the CHOP protein expression and FACS analysis. This is very different from C2C12, the myogenic counterpart of 3T3-L1, which showed significant apoptosis along with ER stress. This study also characterizes a potential mechanism whereby adipocyte may avoid apoptosis to sustain the pathological state of obesity. The level of GRP94 expression significantly upholds in 3T3-L1 under tunicamycin treatment compared to preadipocytes and C2C-12. When GRP94 expression was inhibited by siRNA, 3T3-L1 showed a higher level of CHOP expression compared to C2C12 cells. In conclusion, adipocytes exert an anti-apoptotic mechanism under ER stress caused by tunicamycin; thus, apoptotic induction in adipocyte is not a viable anti-obesity option. The unusual level of GRP94 may serve as a key role whereby adipocytes reach to the obesity level circumventing the apoptosis.