Objective： We evaluated the protective effects of berberine （BBR） combined with ginsenoside Rb1 （G-Rb1） on high-fatdiet （HFD）-induced nonalcoholic fatty liver disease （NAFLD） in rats and futher investigated t...Objective： We evaluated the protective effects of berberine （BBR） combined with ginsenoside Rb1 （G-Rb1） on high-fatdiet （HFD）-induced nonalcoholic fatty liver disease （NAFLD） in rats and futher investigated the underlying mechanisms.Methods： Rats were fed an HFD for 6 weeks and then randomly divided into four groups and treated with BBR （50mg/kg）, G-Rb1 （100 mg/kg）, BBR （50 mg/kg） ＋ G-Rb1 （100 mg/kg）, or fenofibrate （40 mg/kg）. Histological examinationof liver tissue was performed. In human hepatocellular carcinoma cells HepG2, protein expression of AMP-activatedprotein kinase （AMPK） and acetyl-CoA carboxylase was detected by western blotting, and the mRNA expression ofcarnitine palmitoyl transferase 1 and 3-hydroxy-3-methyl glutaryl coenzyme A reductase was detected by quantitativePCR. Pharmacokinetic assessments included analysis of bioavailability of BBR and G-Rb1 in vivo and G-Rb1 metabolismby intestinal bacteria in vitro. Results： Compared to the single-use group, BBR combined with G-Rb1 significantlyameliorated hepatic fat accumulation in HFD-induced obese rats, as demonstrated by reduced hepatic triglyceridecontent, and histological evaluation of liver sections. Activation of hepatic AMPK and phosphorylation of acetyl-CoAcarboxylase were significantly elevated in hepatocytes treated with both BBR and G-Rb1. Consistent with the activationof AMPK, the mRNA expression of carnitine palmitoyl transferase 1 was stimulated, while the mRNA expression of3-hydroxy-3-methyl glutaryl coenzyme A reductase was suppressed. Pharmacokinetic analysis revealed that BBRincreased the bioavailability of G-Rb1 in Sprague-Dawley rats. Additionally, BBR prevented degradation of G-Rb1 infecal solution in vitro. Conclusion： BBR combined with G-Rb1 improved NAFLD through the AMPK signaling pathway,and BBR enhanced G-Rb1 bioavailability via promoting the intestinal absorption of G-Rb1. This combination may be auseful therapeutic agent for NAFLD.展开更多
Intramuscular fat （IMF） content in chickens significantly contributes to meat quality. The main objective of this study was to assess the expression of calcineudn （CAN） and Ca^2＋/calmodutin-dependent protein kina...Intramuscular fat （IMF） content in chickens significantly contributes to meat quality. The main objective of this study was to assess the expression of calcineudn （CAN） and Ca^2＋/calmodutin-dependent protein kinase （CAME） in lipogene- sis in chicken muscle. The chickens were slaughtered and sampled at the ages of 4, 8, and 16 weeks, respectively. IMF content and the expression of CaN subunits and CaMK isoforms were measured in thigh muscle tissue. The results showed that the IMF contents were higher in chickens at the age of 16 weeks compared with those in chickens at the ages of 4 and 8 weeks （P〈0.05）. The expression levels of fatty acid synthase （FAS） and fatty acid translocase CD36 （FAT/CD36） mRNA in 16-week-old chickens were all significantly up-regulated compared with those in 4-week-old chickens （P〈0.05）. The mRNA levels of CaNB and CaMK IV in 16-week-old chickens were significantly lower than those in 4-week-old chickens （P〈0.05）. But the CaMK II mRNA levels in 16-week-old chickens were significantly higher than those in 4-week-old chickens （P〈0.05）. To investigate the roles of CaMK and CaN in adipogenesis, SV cells were incubated in standard adipogenesis medium for 24 h and treated with specific inhibitor of CaMK and CaN. The ex- pressions of CCAAT/enhancer binding protein β（C/EBPJ3）, sterol regulatory element- binding protein 1 （SREBP1） and peroxisome proliferation-activated receptor ）, （PPARy） were dramatically enhanced by CsA and CaN inhibitor （P〈0.05）. KN93, a CaMK Ⅱ inhibitor, dramatically repressed the expression of those lipogenic genes （P〈0.05）. All the results above indicated that CaN and CaMK had different effects on adipogenesis in the muscle of chickens.展开更多
文摘Objective： We evaluated the protective effects of berberine （BBR） combined with ginsenoside Rb1 （G-Rb1） on high-fatdiet （HFD）-induced nonalcoholic fatty liver disease （NAFLD） in rats and futher investigated the underlying mechanisms.Methods： Rats were fed an HFD for 6 weeks and then randomly divided into four groups and treated with BBR （50mg/kg）, G-Rb1 （100 mg/kg）, BBR （50 mg/kg） ＋ G-Rb1 （100 mg/kg）, or fenofibrate （40 mg/kg）. Histological examinationof liver tissue was performed. In human hepatocellular carcinoma cells HepG2, protein expression of AMP-activatedprotein kinase （AMPK） and acetyl-CoA carboxylase was detected by western blotting, and the mRNA expression ofcarnitine palmitoyl transferase 1 and 3-hydroxy-3-methyl glutaryl coenzyme A reductase was detected by quantitativePCR. Pharmacokinetic assessments included analysis of bioavailability of BBR and G-Rb1 in vivo and G-Rb1 metabolismby intestinal bacteria in vitro. Results： Compared to the single-use group, BBR combined with G-Rb1 significantlyameliorated hepatic fat accumulation in HFD-induced obese rats, as demonstrated by reduced hepatic triglyceridecontent, and histological evaluation of liver sections. Activation of hepatic AMPK and phosphorylation of acetyl-CoAcarboxylase were significantly elevated in hepatocytes treated with both BBR and G-Rb1. Consistent with the activationof AMPK, the mRNA expression of carnitine palmitoyl transferase 1 was stimulated, while the mRNA expression of3-hydroxy-3-methyl glutaryl coenzyme A reductase was suppressed. Pharmacokinetic analysis revealed that BBRincreased the bioavailability of G-Rb1 in Sprague-Dawley rats. Additionally, BBR prevented degradation of G-Rb1 infecal solution in vitro. Conclusion： BBR combined with G-Rb1 improved NAFLD through the AMPK signaling pathway,and BBR enhanced G-Rb1 bioavailability via promoting the intestinal absorption of G-Rb1. This combination may be auseful therapeutic agent for NAFLD.
基金Supported by Natural Science Foundation of Hubei Province of China(2011CDB012)Project of State Key Laboratory of Animal Nutrition(2004DA125184F1012)
文摘Intramuscular fat （IMF） content in chickens significantly contributes to meat quality. The main objective of this study was to assess the expression of calcineudn （CAN） and Ca^2＋/calmodutin-dependent protein kinase （CAME） in lipogene- sis in chicken muscle. The chickens were slaughtered and sampled at the ages of 4, 8, and 16 weeks, respectively. IMF content and the expression of CaN subunits and CaMK isoforms were measured in thigh muscle tissue. The results showed that the IMF contents were higher in chickens at the age of 16 weeks compared with those in chickens at the ages of 4 and 8 weeks （P〈0.05）. The expression levels of fatty acid synthase （FAS） and fatty acid translocase CD36 （FAT/CD36） mRNA in 16-week-old chickens were all significantly up-regulated compared with those in 4-week-old chickens （P〈0.05）. The mRNA levels of CaNB and CaMK IV in 16-week-old chickens were significantly lower than those in 4-week-old chickens （P〈0.05）. But the CaMK II mRNA levels in 16-week-old chickens were significantly higher than those in 4-week-old chickens （P〈0.05）. To investigate the roles of CaMK and CaN in adipogenesis, SV cells were incubated in standard adipogenesis medium for 24 h and treated with specific inhibitor of CaMK and CaN. The ex- pressions of CCAAT/enhancer binding protein β（C/EBPJ3）, sterol regulatory element- binding protein 1 （SREBP1） and peroxisome proliferation-activated receptor ）, （PPARy） were dramatically enhanced by CsA and CaN inhibitor （P〈0.05）. KN93, a CaMK Ⅱ inhibitor, dramatically repressed the expression of those lipogenic genes （P〈0.05）. All the results above indicated that CaN and CaMK had different effects on adipogenesis in the muscle of chickens.
