Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strateg...Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as heat.However,drugs based on adipose tissue thermogenesis have not been successfully approved yet.In current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity mice.Mechanismly,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning resistance.Specifically,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and UCP1.Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation.Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.展开更多
"Jinhua Xiangyuan"(JHXY)is a unique type of Chinese tea made from roasted oolong tea and subsequently fermented by Eurotium cristatum.In this study,we investigated the potential benefits of JHXY on obese rat..."Jinhua Xiangyuan"(JHXY)is a unique type of Chinese tea made from roasted oolong tea and subsequently fermented by Eurotium cristatum.In this study,we investigated the potential benefits of JHXY on obese rats induced by a high-sucrose high-fat diet.JHXY infusion was administered orally at 1.6 g/kg·bw(HI),0.8 g/kg·bw(MI),and 0.4 g/kg·bw(LI)per day for 10 weeks.Weight gain was significantly suppressed without affecting appetite.In the MI and HI groups,JHXY led to a significant reduction in triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C),accompanied by an increase in high-density lipoprotein cholesterol(HDL-C)levels.A significant reduction in white adipose tissue(WAT)index and an increase in brown adipose tissue(BAT)index were observed.In MI group,the morphology of hepatocytes was restored.The abundance of Bifidobacterium was elevated,whereas the abundance of Desulfovibrio was significantly reduced.Correlation analysis revealed that the ratio of Ruminococcus to Bifidobacterium was positively correlated with HDL-C;the abundance of the Christensenellaceae_R-7_group was negatively correlated with TC and LDL-C,while positively correlated with HDL-C;the abundance of Lactobacillus was positively correlated with BAT/WAT ratio.In the MI group,the lipopolysaccharide biosynthesis pathway was predicted to be significantly weakened(p<0.05);in the HI group,the sulfur relay system pathway was attenuated,whereas the bacterial toxins pathway was augmented(p<0.05).Our research showed that JHXY has the potential to enhance metabolic health and maintain intestinal homeostasis.Optimal dosage should be a focal point in future research.展开更多
基金funded by National Natural Science Foundation of China(NSFC 82070877)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M-JB-010,2021-I2M-1-005)The National High Technology Research and Development Program of China(2017YFE0112900).
文摘Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as heat.However,drugs based on adipose tissue thermogenesis have not been successfully approved yet.In current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity mice.Mechanismly,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning resistance.Specifically,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and UCP1.Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation.Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.
基金funded by Applied Basic Research Project of COFCO(2017-C1-T06)Yunnan Province Science and Technology Project(202102AE090038).
文摘"Jinhua Xiangyuan"(JHXY)is a unique type of Chinese tea made from roasted oolong tea and subsequently fermented by Eurotium cristatum.In this study,we investigated the potential benefits of JHXY on obese rats induced by a high-sucrose high-fat diet.JHXY infusion was administered orally at 1.6 g/kg·bw(HI),0.8 g/kg·bw(MI),and 0.4 g/kg·bw(LI)per day for 10 weeks.Weight gain was significantly suppressed without affecting appetite.In the MI and HI groups,JHXY led to a significant reduction in triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C),accompanied by an increase in high-density lipoprotein cholesterol(HDL-C)levels.A significant reduction in white adipose tissue(WAT)index and an increase in brown adipose tissue(BAT)index were observed.In MI group,the morphology of hepatocytes was restored.The abundance of Bifidobacterium was elevated,whereas the abundance of Desulfovibrio was significantly reduced.Correlation analysis revealed that the ratio of Ruminococcus to Bifidobacterium was positively correlated with HDL-C;the abundance of the Christensenellaceae_R-7_group was negatively correlated with TC and LDL-C,while positively correlated with HDL-C;the abundance of Lactobacillus was positively correlated with BAT/WAT ratio.In the MI group,the lipopolysaccharide biosynthesis pathway was predicted to be significantly weakened(p<0.05);in the HI group,the sulfur relay system pathway was attenuated,whereas the bacterial toxins pathway was augmented(p<0.05).Our research showed that JHXY has the potential to enhance metabolic health and maintain intestinal homeostasis.Optimal dosage should be a focal point in future research.