Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free ...Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states.Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress.And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance.However,negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications.Furthermore,it appears that oxidative stress is only one of the factors contributing to diabetic complications.Thus,antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.展开更多
One major function of adipocytes is to store excess energy in the form of triglycerides. Insufficient adipose lipid storage is asso- ciated with many pathological conditions including hyperlipidemia, insulin resistanc...One major function of adipocytes is to store excess energy in the form of triglycerides. Insufficient adipose lipid storage is asso- ciated with many pathological conditions including hyperlipidemia, insulin resistance, and type 2 diabetes. In this study, we observed the overexpression of SUMO-specific protease 2 （Senp2） in adipose tissues during obesity. Adipocyte 5enp2 deficiency resulted in less adipose lipid storage accompanied by an ectopic fat accumulation and insulin resistance under high-fat diet feeding. We further found that SET domain bifurcated 1 （Setdbl） was a SUMOylated protein and that SUMOylation promoted Setdbl occupancy on the promoter locus of Pparg and Cebpa genes to suppress their expressions by H3Kgme3. Senp2 could suppress Setdbl function by de-SUMOylation. In adipocyte 5enp2-deficiency mice, accumulation of the SUMOylated Setdbl suppressed the expression of Pparg and Cebpo genes as welt as lipid metabolism-related target genes, which would decrease the ability of lipid storage in adipocytes. These results revealed the crucial role of Senp2-Setdbl axis in controlling adipose lipid storage.展开更多
基金Supported by grant from the National Basic Research Program (973Program) (2006CB503903)
文摘Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states.Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress.And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance.However,negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications.Furthermore,it appears that oxidative stress is only one of the factors contributing to diabetic complications.Thus,antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.
基金This work was supported by grants from the National Natural Science Foundation of China （91019021 and 81430069 to J.C.）, the National Basic Research Program of China （973 Program） （2013CB910902 to J.C.）, Shanghai Committee of Science and Technology （15ZR1424500 to T.W. and 15140904300）, Shanghai Municipal Education Commission （ZZjdyx15003 to T.W. and 2017-01-07-00-01-E00050 to J.C.）, and Shanghai Jiao Tong University School of Medicine （14XJ10001 to T.W.）.
文摘One major function of adipocytes is to store excess energy in the form of triglycerides. Insufficient adipose lipid storage is asso- ciated with many pathological conditions including hyperlipidemia, insulin resistance, and type 2 diabetes. In this study, we observed the overexpression of SUMO-specific protease 2 （Senp2） in adipose tissues during obesity. Adipocyte 5enp2 deficiency resulted in less adipose lipid storage accompanied by an ectopic fat accumulation and insulin resistance under high-fat diet feeding. We further found that SET domain bifurcated 1 （Setdbl） was a SUMOylated protein and that SUMOylation promoted Setdbl occupancy on the promoter locus of Pparg and Cebpa genes to suppress their expressions by H3Kgme3. Senp2 could suppress Setdbl function by de-SUMOylation. In adipocyte 5enp2-deficiency mice, accumulation of the SUMOylated Setdbl suppressed the expression of Pparg and Cebpo genes as welt as lipid metabolism-related target genes, which would decrease the ability of lipid storage in adipocytes. These results revealed the crucial role of Senp2-Setdbl axis in controlling adipose lipid storage.
