AIM:To assess the regulatory effect of micro RNA-185(mi R-185)on lipid metabolism and the insulin signalling pathway in human Hep G2 hepatocytes and a high-fat diet mouse model.METHODS:Quantitative reverse transcripti...AIM:To assess the regulatory effect of micro RNA-185(mi R-185)on lipid metabolism and the insulin signalling pathway in human Hep G2 hepatocytes and a high-fat diet mouse model.METHODS:Quantitative reverse transcription-polymerase chain reaction was used to assess the m RNA levels of lipogenic genes after loss or gain of mi R-185.In addition,the amounts of insulin signalling intermediates were determined after transfection of Hep G2 cells with pre-mi R-185.RESULTS:Mi R-185 levels decreased in a time-and dose-dependent manner in response to palmitic acid in human Hep G2 hepatocytes.Transfection of Hep G2 cells with mi R-185 significantly decreased the m RNA levels of fatty acid synthase,3-hydroxy-3-methylglutaryl-Co A reductase,sterol-regulatory element binding protein-2,and sterol-regulatory element binding protein-1c,whereas inhibition of mi R-185 using an anti-mi R-185oligonucleotide produced the opposite effect in Hep G2cells.In a high-fat diet mouse model,the accumulation of lipids was significantly improved after treatment with mi R-185,compared with control animals.Induction of mi R-185 enhanced the insulin signalling pathway by upregulating the insulin-receptor substrate-2.CONCLUSION:These findings suggest that mi R-185plays an important role in regulating fatty-acid metabolism and cholesterol homeostasis in hepatocytes,as well as in improving insulin sensitivity,both in vitro and in vivo.展开更多
The mechanisms that regulate disease progression during hepatitis C virus(HCV)infection and the response to treatment are not clearly identified.Numerous studies have demonstrated that a strong host immune response ag...The mechanisms that regulate disease progression during hepatitis C virus(HCV)infection and the response to treatment are not clearly identified.Numerous studies have demonstrated that a strong host immune response against HCV favors HCV clearance.In addition,genetic factors and metabolic machinery,particularly cholesterol modulation,are involved in HCV infection.It is likely that the interplay between all of these factors contributes to the outcome of HCV infection.In recent years,the world has experienced its largest epidemic of obesity.Mexico and the United States are the leading sufferers from this epidemic at the global level.Obesity is associated with the development ofnumerous pathologies including hypercholesterolemia which is one of the eight most important risk factors for mortality in Mexico.This may be related to the course of HCV infection in this population.Here,we focus on the urgent need to study the progression of HCV infection in relation to ethnic characteristics.Discoveries are discussed that hold promise in identifying immune,metabolic and genetic factors that,in conjunction,could be therapeutic targets or predictors of the progression of HCV infection.展开更多
基金Supported by National Natural Science Foundation of China,No.30950005the Department of Education of Heilongjiang Province,No.12511233
文摘AIM:To assess the regulatory effect of micro RNA-185(mi R-185)on lipid metabolism and the insulin signalling pathway in human Hep G2 hepatocytes and a high-fat diet mouse model.METHODS:Quantitative reverse transcription-polymerase chain reaction was used to assess the m RNA levels of lipogenic genes after loss or gain of mi R-185.In addition,the amounts of insulin signalling intermediates were determined after transfection of Hep G2 cells with pre-mi R-185.RESULTS:Mi R-185 levels decreased in a time-and dose-dependent manner in response to palmitic acid in human Hep G2 hepatocytes.Transfection of Hep G2 cells with mi R-185 significantly decreased the m RNA levels of fatty acid synthase,3-hydroxy-3-methylglutaryl-Co A reductase,sterol-regulatory element binding protein-2,and sterol-regulatory element binding protein-1c,whereas inhibition of mi R-185 using an anti-mi R-185oligonucleotide produced the opposite effect in Hep G2cells.In a high-fat diet mouse model,the accumulation of lipids was significantly improved after treatment with mi R-185,compared with control animals.Induction of mi R-185 enhanced the insulin signalling pathway by upregulating the insulin-receptor substrate-2.CONCLUSION:These findings suggest that mi R-185plays an important role in regulating fatty-acid metabolism and cholesterol homeostasis in hepatocytes,as well as in improving insulin sensitivity,both in vitro and in vivo.
基金Supported by The National Council of Science and Technol-ogy(CONACYT-FONDO SECTORIAL,Mexico),Grant No.Salud-2010-1-139085 to Roman SCONACYT-CIENCIA BA-SICA,Mexico,Grant No.127229,COECYTJAL-UDG,Mexico,Grants No.S-2010-1-849,CONACYT-INFR,Mexico and Grant No.188240 to Fierro NA
文摘The mechanisms that regulate disease progression during hepatitis C virus(HCV)infection and the response to treatment are not clearly identified.Numerous studies have demonstrated that a strong host immune response against HCV favors HCV clearance.In addition,genetic factors and metabolic machinery,particularly cholesterol modulation,are involved in HCV infection.It is likely that the interplay between all of these factors contributes to the outcome of HCV infection.In recent years,the world has experienced its largest epidemic of obesity.Mexico and the United States are the leading sufferers from this epidemic at the global level.Obesity is associated with the development ofnumerous pathologies including hypercholesterolemia which is one of the eight most important risk factors for mortality in Mexico.This may be related to the course of HCV infection in this population.Here,we focus on the urgent need to study the progression of HCV infection in relation to ethnic characteristics.Discoveries are discussed that hold promise in identifying immune,metabolic and genetic factors that,in conjunction,could be therapeutic targets or predictors of the progression of HCV infection.
