Regulation And Mechanism Of TIGAR On Lipid Metabolism

Aim:TIGAR transgenic mice were used to observe the effects of TIGAR on the lipid metabolism in mice.In vitro,3T3-L1 adipocytes were used to further explore the mechanisms by which TIGAR affects lipid metabolism.Methods:The model of TIGAR transgenic mice was constructed in vivo.The 5 weeks old wild-type mice and TIGAR transgenic mice born in the same nest were fed for 16 weeks under the same condition.The weight,diet and water consumption of each group of mice were measured at the same time.The glucose tolerance and insulin resistance of 8-week-old mice were measured by blood glucose measurement.Indirect calorimetry was used to measure the energy indexes(oxygen consumption,carbon dioxide production,respiration rate and energy consumption)of 8-week-old mice;TC,TG,LDL-C and HDL-C kits were applied to detect the influence of TIGAR on blood lipid;The weight of fat in different parts(epididymis,subcutaneous,retroperitoneal,brown fat)and liver of mice were measured.The size,quantity and damage of fat were observed by H&E and oil red O staining;RT-PCR and Western blot were used to detect the expression of mRNA and protein related to lipogenesis and lipolysis by the overexpression of TIGAR.Conventional culture and differentiation of 3T3-L1 preadipocytes in vitro.The small RNA interference chain was transferred into the cells by liposome method,observation of the effect of TIGAR knockdown on the number and size of lipid droplets by oil red O staining;RT-PCR and Western blot were used to detect the expression of mRNA and protein related to lipogenesis and lipolysis by the knockdown of TIGAR.Results:In vivo,compared with wild-type mice,the body weight of TIGAR transgenic mice was significantly increased(P<0.05),the glucose tolerance and insulin sensitivity were decreased(P<0.01);TIGAR transgenic mice had higher oxygen consumption and carbon dioxide production(P<0.05),but there was no significant difference in energy consumption and breathing rate(P>0.05);There were significant increases in the weight of fat tissue and liver,lipid drops and liver damage in TIGAR transgenic mice(P<0.01);TIGAR transgenic mice increased the levels of blood glucose and blood lipid(P<0.01);The mRNA levels and protein expression of lipogenesis related factors increased(FAS,ACC,PPAR-y)and the mRNA level and protein expression level of fat decomposition related factors decreased(HSL,ACOX)in TIGAR transgenic mice(P<0.05).In vitro,TIGAR knockdown could decrease lipid droplets,mRNA levels and protein expression of lipogenesis related factors,but the mRNA levels and protein expression of lipolysis related factors increased(P<0.05).Conclusions:Compared with wild-type mice,TIGAR transgenic mice had increased body weight,food and water intake,increased content of adipose tissue and liver with different degrees of damage,increased blood lipid and glucose,decreased glucose tolerance and sensitivity of insulin,accelerated oxygen expenditure and carbon dioxide outout.Overexpression of TIGAR was conducive to fat synthesis and inhibition of fat decomposition.In this study,we focused on the direct regulation of TIGAR on fat synthetase and catabolic enzyme to find out the new function of TIGAR,which provided a new concept for regulation of lipid metabolism and prevention of obesity.