Endometrial carcinoma(EMC)is associated with obesity;however,the underlying mechanisms have not yet been elucidated.Peroxisome proliferator-activated receptor alpha(PPARα)is a nuclear receptor that is involved in lip...Endometrial carcinoma(EMC)is associated with obesity;however,the underlying mechanisms have not yet been elucidated.Peroxisome proliferator-activated receptor alpha(PPARα)is a nuclear receptor that is involved in lipid,glucose,and energy metabolism.PPARαreportedly functions as a tumor suppressor through its effects on lipid metabolism;however,the involvement of PPARαin the development of EMC remains unclear.The present study demonstrated that the immunohistochemical expression of nuclear PPARαwas lower in EMC than in normal endometrial tissues,suggesting the tumor suppressive nature of PPARα.A treatment with the PPARαactivator,irbesartan,inhibited the EMC cell lines,Ishikawa and HEC1A,by down-regulating sterol regulatory element-binding protein 1(SREBP1)and fatty acid synthase(FAS)and up-regulating the tumor suppressor genes p21 and p27,antioxidant enzymes,and AT-rich interaction domain 1A(ARID1A).These results indicate the potential of the activation of PPARαas a novel therapeutic approach against EMC.展开更多
Nonalcoholic fatty liver disease(NAFLD) and type 2 Diabetes Mellitus(T2 DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2 DM patients. In Asian traditional me...Nonalcoholic fatty liver disease(NAFLD) and type 2 Diabetes Mellitus(T2 DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2 DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2 DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract(MCE; 10 g·kg-1·d-1) lowered the blood lipid levels and reversed insulin resistance(IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1 c(SREBP-1 c) and carbohydrate-responsive element binding protein(Ch REBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and m RNA expression levels of SREBP-1 c and Ch REBP. In conclusion, down-regulation of SREBP-1 c and Ch REBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2 DM associated with NAFLD.展开更多
基金supported by JSPS KAKENHI Grant Number 18K09285.
文摘Endometrial carcinoma(EMC)is associated with obesity;however,the underlying mechanisms have not yet been elucidated.Peroxisome proliferator-activated receptor alpha(PPARα)is a nuclear receptor that is involved in lipid,glucose,and energy metabolism.PPARαreportedly functions as a tumor suppressor through its effects on lipid metabolism;however,the involvement of PPARαin the development of EMC remains unclear.The present study demonstrated that the immunohistochemical expression of nuclear PPARαwas lower in EMC than in normal endometrial tissues,suggesting the tumor suppressive nature of PPARα.A treatment with the PPARαactivator,irbesartan,inhibited the EMC cell lines,Ishikawa and HEC1A,by down-regulating sterol regulatory element-binding protein 1(SREBP1)and fatty acid synthase(FAS)and up-regulating the tumor suppressor genes p21 and p27,antioxidant enzymes,and AT-rich interaction domain 1A(ARID1A).These results indicate the potential of the activation of PPARαas a novel therapeutic approach against EMC.
基金supported by Ningbo Science and Technology Innovation Team Program(No.2014B82002)the National Natural Science Foundation of China(Nos.81370165,81501421,and 31301068)+1 种基金the Natural Science Foundation of Ningbo(Nos.2013A610209 and 2015A610217)Fang Runhua Fund of Hong Kong and K.C.Wong Magna Fund of Ningbo University
文摘Nonalcoholic fatty liver disease(NAFLD) and type 2 Diabetes Mellitus(T2 DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2 DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2 DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract(MCE; 10 g·kg-1·d-1) lowered the blood lipid levels and reversed insulin resistance(IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1 c(SREBP-1 c) and carbohydrate-responsive element binding protein(Ch REBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and m RNA expression levels of SREBP-1 c and Ch REBP. In conclusion, down-regulation of SREBP-1 c and Ch REBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2 DM associated with NAFLD.
