Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component ...Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component of staple foods that are consumed daily,and the effects,metabolic pathway,and molecular mechanism of starch in the context of NAFLD remain unclear.Our study showed that a high-starch carbohydrate diet(HCD)led to the occurrence and exacerbation of NAFLD in mice.Transcriptomics and metabonomic analyses showed that the increased fatty acid influx mediated by NADPH oxidase 2(NOX2)exacerbated NAFLD.Knocking down NOX2 specifically alleviated HCD-induced NAFLD in vivo and in vitro.Moreover,the large amounts of ROS produced by NOX2 further exacerbated insulin resistance and increased lipolysis in perirenal white adipose tissue(periWAT),thereby providing fatty acids for hepatic lipid synthesis.In addition,the interaction between AMPKα1 and p47phox was the pathway that mediated the high expression of NOX2 induced by a HCD.Our study systematically demonstrated the effect of a HCD on NAFLD.Elevated fatty acid influx is a unique molecular regulatory pathway that mediates HCD-induced NAFLD exacerbation,which is different from the effect of simple sugars.Additionally,NOX2 was suggested to be a specific and effective drug target for NAFLD.展开更多
Objective To explore the effects of zinc-0t2-glycoprotein （ZAG） on body weight and body fat in high-fat-diet （HF1））-induced obesity in mice and the possible mechanism. Methods Thirty-six male mice were fed with ...Objective To explore the effects of zinc-0t2-glycoprotein （ZAG） on body weight and body fat in high-fat-diet （HF1））-induced obesity in mice and the possible mechanism. Methods Thirty-six male mice were fed with standard food （SF） （n=9） and HFD （n=27）, respectively. Five weeks later, 9 mice fed with HFD were subjected to ZAG expression plasmid DNA transfection by liposome transfection method, and another 9 mice to negative control plasmid transfection. Two weeks later, serum ZAG level in the mice was assayed by Western blot, and the effects of ZAG over-expression on body weight, body fat, serum biochemical indexes, and adipose tissue of obese mice were evaluated. The mRNA expressions of fatty acid synthase （FAS） and hormone sensitive lipase （HSL） in liver tissue were deterlnined by reverse transcription-polymerase chain reaction. Results Serum ZAG level significantly lowered in simple HFD-fed mice in comparison to SF-fed mice （0.51±0.10 AU vs. 0.75±0.07 AU, P〈0.01）. Further statistical analysis demonstrated that ZAG level was negatively correlated with body weight （r =-0.56, P〈0.001）, epididymal fat mass （r=-0.67, P〈O. 001）, percentage of epididymal fat （r= 0.65, P〈0.001）, and increased weight （r= 0.57, P〈0.001） in simple SF- and HFD fed mice. ZAG over-expression in obese mice reduced body weight and the percentage of epididyreal fat. Furthermore, FAS mRNA expression decreased （P〈0.01） and HSL mRNA expression increased （P〈0.001） in the liver in ZAG over-expressing mice. Conclusions ZAG is closely related to obesity. Serum ZAG level is inversely correlated with body weight and percentage of body fat. The action of ZAG is associated with reduced FAS expression and increased HSL expression in the liver of obese mice.展开更多
基金financially supported by grants from the National Natural Science Foundation of China(8217087381871095)+1 种基金the National Key R&D Program of China(2018YFC2000304)the Tsinghua University Spring Breeze Fund(20211080005).
文摘Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component of staple foods that are consumed daily,and the effects,metabolic pathway,and molecular mechanism of starch in the context of NAFLD remain unclear.Our study showed that a high-starch carbohydrate diet(HCD)led to the occurrence and exacerbation of NAFLD in mice.Transcriptomics and metabonomic analyses showed that the increased fatty acid influx mediated by NADPH oxidase 2(NOX2)exacerbated NAFLD.Knocking down NOX2 specifically alleviated HCD-induced NAFLD in vivo and in vitro.Moreover,the large amounts of ROS produced by NOX2 further exacerbated insulin resistance and increased lipolysis in perirenal white adipose tissue(periWAT),thereby providing fatty acids for hepatic lipid synthesis.In addition,the interaction between AMPKα1 and p47phox was the pathway that mediated the high expression of NOX2 induced by a HCD.Our study systematically demonstrated the effect of a HCD on NAFLD.Elevated fatty acid influx is a unique molecular regulatory pathway that mediates HCD-induced NAFLD exacerbation,which is different from the effect of simple sugars.Additionally,NOX2 was suggested to be a specific and effective drug target for NAFLD.
基金Supported by the National Natural Science Foundation of China (30771026)Beijing Natural Science Foundation (7082079)
文摘Objective To explore the effects of zinc-0t2-glycoprotein （ZAG） on body weight and body fat in high-fat-diet （HF1））-induced obesity in mice and the possible mechanism. Methods Thirty-six male mice were fed with standard food （SF） （n=9） and HFD （n=27）, respectively. Five weeks later, 9 mice fed with HFD were subjected to ZAG expression plasmid DNA transfection by liposome transfection method, and another 9 mice to negative control plasmid transfection. Two weeks later, serum ZAG level in the mice was assayed by Western blot, and the effects of ZAG over-expression on body weight, body fat, serum biochemical indexes, and adipose tissue of obese mice were evaluated. The mRNA expressions of fatty acid synthase （FAS） and hormone sensitive lipase （HSL） in liver tissue were deterlnined by reverse transcription-polymerase chain reaction. Results Serum ZAG level significantly lowered in simple HFD-fed mice in comparison to SF-fed mice （0.51±0.10 AU vs. 0.75±0.07 AU, P〈0.01）. Further statistical analysis demonstrated that ZAG level was negatively correlated with body weight （r =-0.56, P〈0.001）, epididymal fat mass （r=-0.67, P〈O. 001）, percentage of epididymal fat （r= 0.65, P〈0.001）, and increased weight （r= 0.57, P〈0.001） in simple SF- and HFD fed mice. ZAG over-expression in obese mice reduced body weight and the percentage of epididyreal fat. Furthermore, FAS mRNA expression decreased （P〈0.01） and HSL mRNA expression increased （P〈0.001） in the liver in ZAG over-expressing mice. Conclusions ZAG is closely related to obesity. Serum ZAG level is inversely correlated with body weight and percentage of body fat. The action of ZAG is associated with reduced FAS expression and increased HSL expression in the liver of obese mice.
