Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which ...Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which enhances oxidative stress and tipogenesis in NAFLD.The forkhead transcription factor O1 （FoxO1） is another important gene involved in NAFLD,which causes lipid disorders when insulin resistance appears in the liver.However,the interactions between FTO and FoxO1 during the pathogenesis of NAFLD have not been fully elucidated.This study was designed to identify the relationship between these two factors that are involved in the development of NAFLD.Methods This study includes two parts referred to as animal and cell experiments.Twelve female SPF C57BL/6 mice were fed a high-fat diet to serve as an NAFLD animal model.Aspartate aminotransferase （AST）,alanine aminotransferase （ALT）,total triglyceride （TG）,total cholesterol （TC）,alkaline phosphatase （ALP）,high-density lipoprotein （HDL）,and low-density lipoprotein （LDL） were measured.Immunohistochemical analysis was used to detect the expression and histological localization of FTO,FoxO1,and adenosine monophosphate （AMP）-activated protein kinase （AMPK）.The L02 cells were exposed to high fat for 24,48,or 72 hours.Oil red O staining was used to detect intracellular lipid droplets.Reverse transcription-polymerase chain reaction was used for analyzing the levels of FTO and FoxO1 mRNA.Results At the end of 10 weeks,ALP,ALT,AST,and LDL were significantly increased （P ＜0.01）,while TC and TG were also significantly higher （P ＜0.05）.In addition,HDL was significantly decreased （P ＜0.05）.The FTO and FoxO1 proteins were weakly expressed in the control group,but both FTO and FoxO1 were expressed significantly higher （P ＜0.01） in the experimental group,and the expression of the two factors was significantly correlated.AMPK in the high-fat group showed a low level of correlation with FTO,but not with FoxO1.Oil Red O staining results showed that the cells cultured in 50％ fetal bovine serum for 24,48,or 72 hours exhibited steatosis.FTO and FoxO1 mRNA were increased in the high-fat group compared with the normal group （P ＜0.01）.The expression levels of FTO and FoxO1 mRNA were the highest at 48 hours （P ＜0.05）.Conclusions A high-fat diet leads to higher expression of FTO,phosphorylation of FoxO1,and decreased phosphorylation of AMPK.These results suggest that the interactions between FTO and FoxO1 are closely related to the pathogenesis of NAFLD.展开更多
Cardiolipin （CL） is a phospholipid exclusively localized in inner mitochondrial membrane where it is required for oxidative phosphorylation, ATP synthesis, and mitochondrial bioenergetics. The biological functions o...Cardiolipin （CL） is a phospholipid exclusively localized in inner mitochondrial membrane where it is required for oxidative phosphorylation, ATP synthesis, and mitochondrial bioenergetics. The biological functions of CL are thought to depend on its acyl chain composition which is dominated by linoleic acids in metabolically active tissues. This unique feature is not derived from the de novo biosynthesis of CL, rather from a remodeling process that involves in phospholipases and transacylase/acyltransferase. The remodeling process is also believed to be responsible for generation of CL species that causes oxidative stress and mitochondrial dysfunction. CL is highly sensitive to oxidative damages by reactive oxygen species （ROS） due to its high content in polyunsaturated fatty acids and location near the site of ROS production. Consequently, pathological remodeling of CL has been implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, heart failure, neurodegeneration, and aging that are characterized by oxidative stress, CL deficiency, and abnormal CL species. This review summarizes recent progresses in molecular, enzymatic, lipidomic, and metabolic studies that support a critical regulatory role of pathological CL remodeling as a missing link between oxidative stress and mitochondrial dysfunction in metabolic diseases and aging.展开更多
To investigate the role of gene variants and derived haplotypes of the CLOCK transcription factor in nonalcoholic fatty liver disease （NAFID） and their relation with the disease severity.METHODS： A total of 136 pat...To investigate the role of gene variants and derived haplotypes of the CLOCK transcription factor in nonalcoholic fatty liver disease （NAFID） and their relation with the disease severity.METHODS： A total of 136 patients with NAFLD and 64 healthy individuals were studied. Liver biopsy was performed in 91 patients. Six tag SNPs showing a minor allele frequency 〉 10% （rs1554483 C/G; rs11932595 A/G; rs4580704 C/G; rs6843722 A/C; rs6850524 C/G and rs4864548 A/G） encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites （P 〉 0.8） were genotyped. RESULTS： rs11932595 and rs6843722 showed significant associations with NAFLD （empiric P = 0.0449 and 0.023, respectively）. A significant association was also observed between clinical or histologic spectrum of NAFLD and rs1554483 （empiric P = 0.0399）, rs6843722 （empiric P = 0.0229） and rs6850524 （empiric P = 0.00899） and between fibrosis score and rs1554483 （empiric P = 0.02697）, rs6843722 （empiric P = 0.01898） and rs4864548 （empiric P = 0.02697）. Test of haplotypic association showed that CLOCK gene variant haplotypes frequencies in NAFLD individuals significantly differed from those in controls （empiric P = 0.0097）.CONCLUSION： Our study suggests a potential role of the CLOCK polymorphisms and their haplotypes insusceptibility to NAFLD and disease severity.展开更多
Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the mos...Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver.展开更多
Most medical specialties including the field of gastroenterology are mainly aimed at treating diseases rather than preventing them. Genomic medicine studies the health/disease process based on the interaction of the h...Most medical specialties including the field of gastroenterology are mainly aimed at treating diseases rather than preventing them. Genomic medicine studies the health/disease process based on the interaction of the human genes with the environment. The gastrointestinal(GI) system is an ideal model to analyze the interaction between our genes, emotions and the gut microbiota. Based on the current knowledge, this mini-review aims to provide an integrated synopsis of this interaction to achieve a better understanding of the GI disorders related to bad eating habits and stress-related disease. Since human beings are the result of an evolutionary process, many biological processes such as instincts, emotions and behavior are interconnected to guarantee survival. Nourishment is a physiological need triggered by the instinct of survival to satisfy the body's energy demands. The brain-gut axis comprises a tightly connected neuralneuroendocrine circuitry between the hunger-satiety center, the dopaminergic reward system involved in the pleasure of eating and the gut microbiota that regulates which food we eat and emotions. However, genetic variations and the consumption of high-sugar and high-fat diets have overridden this energy/pleasure neurocircuitry to the point of addiction of several foodstuffs. Consequently, a gut dysbiosis generates inflammation and a negative emotional state may lead to chronic diseases. Balancing this altered processes to regain health may involve personalized-medicine and genome-based strategies. Thus, an integrated approach based on the understanding of the gene-emotions-gut microbiota interaction is the next frontier that awaits the gastroenterologist to prevent and treat GI disorders associated with obesity and negative emotions.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a global health issue that is correlated with obesity and oxidative stress.AIM To evaluate the anti-NAFLD effect of papaya in high fat diet induced obesity in rats...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a global health issue that is correlated with obesity and oxidative stress.AIM To evaluate the anti-NAFLD effect of papaya in high fat diet induced obesity in rats.METHODS Four-week-old male Sprague-Dawley rats were divided into four groups after 1 wk of acclimatization:Group 1 was the rats fed a normal diet(C);group 2 was the rats fed a high fat diet(HFD);group 3 was the rats fed a HFD with 0.5 mL of papaya juice/100 g body weight(HFL),and group 4 was the rats fed a HFD with 1 mL of papaya juice/100 g body weight(HFH)for 12 wk.At the end of the treatment,blood and tissue samples were collected for biochemical analyses and histological assessment.RESULTS The results of the HFH group showed significantly reduced body weight(HFH vs HFD,P<0.01),decreased NAFLD score(HFH vs HFD,P<0.05),and reduced hepatic total cholesterol(HFL vs HFD,P<0.01;HFH vs HFD,P<0.001),hepatic triglyceride(HFH vs HFD,P<0.05),malondialdehyde(HFL,HFH vs HFD,P<0.001),tumour necrosis factor-α(HFH vs HFD,P<0.05)and interleukin-6(HFH vs HFD,P<0.05)when compared to the HFD group.However,the liver weight showed no significant difference among the groups.The activities of catalase and superoxide dismutase significantly increased in HFH when compared with the HFD group(P<0.05 and P<0.001,respectively).The suppression of transcriptional factors of hepatic lipogenesis,including sterol regulatory elementbinding protein 1c and fatty acid synthase,were observed in the papaya treated group(HFH vs HFD,P<0.05).These beneficial effects of papaya against HFDinduced NAFLD are through lowering hepatic lipid accumulation,suppressing the lipogenic pathway,improving the balance of antioxidant status,and lowering systemic inflammation.CONCLUSION These current results provide experimental-based evidence suggesting papaya is an efficacious medicinal fruit for use in the prevention or treatment of NAFLD.展开更多
AIM To determine the role of G0/G1 switch gene 2(G0 S2) and its transcriptional regulation in palmitate-induced hepatic lipid accumulation.METHODS Hep G2 cells were treated with palmitate,or palmitate in combination w...AIM To determine the role of G0/G1 switch gene 2(G0 S2) and its transcriptional regulation in palmitate-induced hepatic lipid accumulation.METHODS Hep G2 cells were treated with palmitate,or palmitate in combination with CCAAT/enhancer binding protein(C/EBP)β si RNA or G0 S2 si RNA. The m RNA expression of C/EBPβ,peroxisome proliferator-activated receptor(PPAR)γ and PPARγ target genes(G0 S2,GPR81,GPR109 A and Adipoq) was examined by q PCR. The protein expression of C/EBPβ,PPARγ,and G0 S2 was determined by Western blotting. Lipid accumulation was detected with Oil Red O staining and quantified by absorbance value of the extracted Oil Red O dye. Lipolysis was evaluated by measuring the amount of glycerol released into the medium. RESULTS Palmitate caused a dose-dependent increase in lipid accumulation and a dose-dependent decrease in lipolysis in Hep G2 cells. In addition,palmitate increased the m RNA expression of C/EBPβ,PPARγ,and PPARγ target genes(G0 S2,GPR81,GPR109 A,and Adipoq) and the protein expression of C/EBPβ,PPARγ,and G0 S2 in a dose-dependent manner. Knockdown of C/EBPβ decreased palmitate-induced PPARγ and its target genes(G0 S2,GPR81,GPR109 A,and Adipoq) m RNA expression and palmitate-induced PPARγ and G0 S2 protein expression in Hep G2 cells. Knockdown of C/EBPβ also attenuated lipid accumulation and augmented lipolysis in palmitate-treated Hep G2 cells. G0 S2 knockdown attenuated lipid accumulation and augmented lipolysis,while G0 S2 knockdown had no effects on the m RNA expression of C/EBPβ,PPARγ,and PPARγ target genes(GPR81,GPR109 A and Adipoq) in palmitate-treated Hep G2 cells. CONCLUSION Palmitate can induce lipid accumulation in Hep G2 cells by activating C/EBPβ-mediated G0 S2 expression.展开更多
目的:探讨脂肪相关基因(fat mass and obesity associated gene,FTO)及其抑制剂大黄酸(rhein)在非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)中的作用。方法:采用高脂饲料喂养的方法构建NAFLD小鼠模型,利用灌胃的方式使...目的:探讨脂肪相关基因(fat mass and obesity associated gene,FTO)及其抑制剂大黄酸(rhein)在非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)中的作用。方法:采用高脂饲料喂养的方法构建NAFLD小鼠模型,利用灌胃的方式使用rhein进行治疗。为评估造模是否成功及药物治疗效果,分别采用H-E染色、油红染色确定小鼠肝细胞中脂肪沉积的情况,采用Western blot检测FTO蛋白在小鼠肝脏组织中的变化情况。结果:与普饲组相比,高脂组小鼠的摄食量明显降低(P<0.01),高脂+rhein组小鼠的体质量明显低于高脂组(P<0.05)。与高脂组相比,高脂+rhein组小鼠肝细胞中脂肪空泡明显减少,高脂组小鼠肝细胞中脂肪沉积明显多于普饲组,rhein灌胃的小鼠肝细胞中脂肪沉积明显减少。与高脂组相比,高脂+rhein组小鼠的脂肪代谢明显恢复。FTO蛋白在高脂组小鼠的肝组织中显著增多,而在高脂+rhein组小鼠肝组织中FTO蛋白的表达量明显回落。结论:Rhein可减少NAFLD小鼠模型中肝组织FTO蛋白的表达,有治疗NAFLD的潜能。展开更多
BACKGROUND Dyslipidemias are metabolic abnormalities associated with chronic diseases caused by genetic and environmental factors.The Mexican population displays regional differences according to ethnicity with an imp...BACKGROUND Dyslipidemias are metabolic abnormalities associated with chronic diseases caused by genetic and environmental factors.The Mexican population displays regional differences according to ethnicity with an impact on the type of dyslipidemia.AIM To define the main dyslipidemias,the frequency of lipid-related risk alleles,and their association with hyperlipidemic states among different ethnic groups in West Mexico.METHODS In a retrospective study,1324 adults were selected to compare dyslipidemias and lipid-related gene polymorphisms.Demographic,clinical,and laboratory data were collected.A subgroup of 196 normal weight subjects without impaired glucose was selected for the association analyses.Genotyping was determined by allelic discrimination assay.RESULTS Hypercholesterolemia was the most prevalent dyslipidemia(42.3%).The frequency of the risk alleles associated with hypoalphalipoproteinemia(ABCA1)and hypercholesterolemia(APOE,LDLR)was higher in the Native Americans(P=0.047).In contrast,the Mestizos with European ancestry showed a higher frequency of the risk alleles for hypertriglyceridemia(APOE2,MTTP)(P=0.045).In normal weight Mestizo subjects,the APOB TT and LDLR GG genotypes were associated risk factors for hypercholesterolemia(OR=5.33,95%CI:1.537-18.502,P=0.008 and OR=3.90,95%CI:1.042-14.583,P=0.043,respectively),and displayed an increase in low-density lipoprotein cholesterol levels(APOB:β=40.39,95%CI:14.415-66.366,P=0.004;LDLR:β=20.77,95%CI:5.763-35.784,P=0.007).CONCLUSION Gene polymorphisms and dyslipidemias showed a differential distribution.Regional primary health care strategies are required to mitigate their prevalence considering the genetic and environmental features which could have important implications for personalized medicine within the new era of precision medicine.展开更多
文摘Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which enhances oxidative stress and tipogenesis in NAFLD.The forkhead transcription factor O1 （FoxO1） is another important gene involved in NAFLD,which causes lipid disorders when insulin resistance appears in the liver.However,the interactions between FTO and FoxO1 during the pathogenesis of NAFLD have not been fully elucidated.This study was designed to identify the relationship between these two factors that are involved in the development of NAFLD.Methods This study includes two parts referred to as animal and cell experiments.Twelve female SPF C57BL/6 mice were fed a high-fat diet to serve as an NAFLD animal model.Aspartate aminotransferase （AST）,alanine aminotransferase （ALT）,total triglyceride （TG）,total cholesterol （TC）,alkaline phosphatase （ALP）,high-density lipoprotein （HDL）,and low-density lipoprotein （LDL） were measured.Immunohistochemical analysis was used to detect the expression and histological localization of FTO,FoxO1,and adenosine monophosphate （AMP）-activated protein kinase （AMPK）.The L02 cells were exposed to high fat for 24,48,or 72 hours.Oil red O staining was used to detect intracellular lipid droplets.Reverse transcription-polymerase chain reaction was used for analyzing the levels of FTO and FoxO1 mRNA.Results At the end of 10 weeks,ALP,ALT,AST,and LDL were significantly increased （P ＜0.01）,while TC and TG were also significantly higher （P ＜0.05）.In addition,HDL was significantly decreased （P ＜0.05）.The FTO and FoxO1 proteins were weakly expressed in the control group,but both FTO and FoxO1 were expressed significantly higher （P ＜0.01） in the experimental group,and the expression of the two factors was significantly correlated.AMPK in the high-fat group showed a low level of correlation with FTO,but not with FoxO1.Oil Red O staining results showed that the cells cultured in 50％ fetal bovine serum for 24,48,or 72 hours exhibited steatosis.FTO and FoxO1 mRNA were increased in the high-fat group compared with the normal group （P ＜0.01）.The expression levels of FTO and FoxO1 mRNA were the highest at 48 hours （P ＜0.05）.Conclusions A high-fat diet leads to higher expression of FTO,phosphorylation of FoxO1,and decreased phosphorylation of AMPK.These results suggest that the interactions between FTO and FoxO1 are closely related to the pathogenesis of NAFLD.
基金supported in part by grants NIH(DK076685,Y.S.)Pennsylvania Department of Health using Tobacco Settlement Funds(10-K-273,Y.S.)
文摘Cardiolipin （CL） is a phospholipid exclusively localized in inner mitochondrial membrane where it is required for oxidative phosphorylation, ATP synthesis, and mitochondrial bioenergetics. The biological functions of CL are thought to depend on its acyl chain composition which is dominated by linoleic acids in metabolically active tissues. This unique feature is not derived from the de novo biosynthesis of CL, rather from a remodeling process that involves in phospholipases and transacylase/acyltransferase. The remodeling process is also believed to be responsible for generation of CL species that causes oxidative stress and mitochondrial dysfunction. CL is highly sensitive to oxidative damages by reactive oxygen species （ROS） due to its high content in polyunsaturated fatty acids and location near the site of ROS production. Consequently, pathological remodeling of CL has been implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, heart failure, neurodegeneration, and aging that are characterized by oxidative stress, CL deficiency, and abnormal CL species. This review summarizes recent progresses in molecular, enzymatic, lipidomic, and metabolic studies that support a critical regulatory role of pathological CL remodeling as a missing link between oxidative stress and mitochondrial dysfunction in metabolic diseases and aging.
基金Supported by Grant B119 (Universidad de Buenos Aires), PICT 25920 (Agencia Nacional de Promoción Científi ca y Tecnológica) and PIP 5195 (Consejo Nacional de Investigaciones Científicas y Técnicas). SS, CG and CJP belong to Consejo Nacional de Investigaciones Científi cas y Técnicas
文摘To investigate the role of gene variants and derived haplotypes of the CLOCK transcription factor in nonalcoholic fatty liver disease （NAFID） and their relation with the disease severity.METHODS： A total of 136 patients with NAFLD and 64 healthy individuals were studied. Liver biopsy was performed in 91 patients. Six tag SNPs showing a minor allele frequency 〉 10% （rs1554483 C/G; rs11932595 A/G; rs4580704 C/G; rs6843722 A/C; rs6850524 C/G and rs4864548 A/G） encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites （P 〉 0.8） were genotyped. RESULTS： rs11932595 and rs6843722 showed significant associations with NAFLD （empiric P = 0.0449 and 0.023, respectively）. A significant association was also observed between clinical or histologic spectrum of NAFLD and rs1554483 （empiric P = 0.0399）, rs6843722 （empiric P = 0.0229） and rs6850524 （empiric P = 0.00899） and between fibrosis score and rs1554483 （empiric P = 0.02697）, rs6843722 （empiric P = 0.01898） and rs4864548 （empiric P = 0.02697）. Test of haplotypic association showed that CLOCK gene variant haplotypes frequencies in NAFLD individuals significantly differed from those in controls （empiric P = 0.0097）.CONCLUSION： Our study suggests a potential role of the CLOCK polymorphisms and their haplotypes insusceptibility to NAFLD and disease severity.
基金Supported by The American Heart Association(13SDG14640038)2012 Yale Center for Clinical Investigation cholar award to Santoro NThis publication was also made possible by CTSA Grant Number UL1 RR024139 from the National Center for Advancing Translational Science,a component of the National Institutes of Health(NIH),and NIH roadmap for Medical Research,Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH
文摘Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver.
基金Supported by Prodep-Universidad de Guadalajara,No.CA-478
文摘Most medical specialties including the field of gastroenterology are mainly aimed at treating diseases rather than preventing them. Genomic medicine studies the health/disease process based on the interaction of the human genes with the environment. The gastrointestinal(GI) system is an ideal model to analyze the interaction between our genes, emotions and the gut microbiota. Based on the current knowledge, this mini-review aims to provide an integrated synopsis of this interaction to achieve a better understanding of the GI disorders related to bad eating habits and stress-related disease. Since human beings are the result of an evolutionary process, many biological processes such as instincts, emotions and behavior are interconnected to guarantee survival. Nourishment is a physiological need triggered by the instinct of survival to satisfy the body's energy demands. The brain-gut axis comprises a tightly connected neuralneuroendocrine circuitry between the hunger-satiety center, the dopaminergic reward system involved in the pleasure of eating and the gut microbiota that regulates which food we eat and emotions. However, genetic variations and the consumption of high-sugar and high-fat diets have overridden this energy/pleasure neurocircuitry to the point of addiction of several foodstuffs. Consequently, a gut dysbiosis generates inflammation and a negative emotional state may lead to chronic diseases. Balancing this altered processes to regain health may involve personalized-medicine and genome-based strategies. Thus, an integrated approach based on the understanding of the gene-emotions-gut microbiota interaction is the next frontier that awaits the gastroenterologist to prevent and treat GI disorders associated with obesity and negative emotions.
基金Supported by National Research Council of Thailand,No.R2560B137(to Tunsophon S)and No.2562/20(to Deenin W)Thailand Research Fund,No.RDG5820017(to Tunsophon S).
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a global health issue that is correlated with obesity and oxidative stress.AIM To evaluate the anti-NAFLD effect of papaya in high fat diet induced obesity in rats.METHODS Four-week-old male Sprague-Dawley rats were divided into four groups after 1 wk of acclimatization:Group 1 was the rats fed a normal diet(C);group 2 was the rats fed a high fat diet(HFD);group 3 was the rats fed a HFD with 0.5 mL of papaya juice/100 g body weight(HFL),and group 4 was the rats fed a HFD with 1 mL of papaya juice/100 g body weight(HFH)for 12 wk.At the end of the treatment,blood and tissue samples were collected for biochemical analyses and histological assessment.RESULTS The results of the HFH group showed significantly reduced body weight(HFH vs HFD,P<0.01),decreased NAFLD score(HFH vs HFD,P<0.05),and reduced hepatic total cholesterol(HFL vs HFD,P<0.01;HFH vs HFD,P<0.001),hepatic triglyceride(HFH vs HFD,P<0.05),malondialdehyde(HFL,HFH vs HFD,P<0.001),tumour necrosis factor-α(HFH vs HFD,P<0.05)and interleukin-6(HFH vs HFD,P<0.05)when compared to the HFD group.However,the liver weight showed no significant difference among the groups.The activities of catalase and superoxide dismutase significantly increased in HFH when compared with the HFD group(P<0.05 and P<0.001,respectively).The suppression of transcriptional factors of hepatic lipogenesis,including sterol regulatory elementbinding protein 1c and fatty acid synthase,were observed in the papaya treated group(HFH vs HFD,P<0.05).These beneficial effects of papaya against HFDinduced NAFLD are through lowering hepatic lipid accumulation,suppressing the lipogenic pathway,improving the balance of antioxidant status,and lowering systemic inflammation.CONCLUSION These current results provide experimental-based evidence suggesting papaya is an efficacious medicinal fruit for use in the prevention or treatment of NAFLD.
文摘非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是全世界最多见和最重要的慢性肝病,由于成人和儿童肥胖流行率增加,其发病率迅速增加,发病率高达17%-33%,且有逐年上升趋势.其中1/3-1/2可能为非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH),单纯性脂肪肝随访10-20年发展为肝硬化的概率为0.6%-3.0%,N A S H随访1 0-1 5年肝硬化的发生率高达15%-25%.发生肝硬化后每年1%病例发生肝细胞癌.有关NAFLD的发病机制迄今尚不完全明了.普遍认为年龄、性别、肥胖、胰岛素抵抗、细胞因子、基因多态性、肠道微生物是主要的发病机制.因此如能全面深入的了解发病机制,可为治疗提供依据.近几年陆续报道用细胞因子或基因为靶点,对NAFLD治疗取得一定疗效,在当前NAFLD尚无特效治疗的情况下,基因或靶向治疗对疾病的预后有可能产生深远的影响.应当着进一步深入的研究.
基金Supported by the grants from the Natural Science Foundation of Shanxi Province,China,No.2014011043-1the Social Development Project of Jinzhong,Shanxi Province,No.S1601
文摘AIM To determine the role of G0/G1 switch gene 2(G0 S2) and its transcriptional regulation in palmitate-induced hepatic lipid accumulation.METHODS Hep G2 cells were treated with palmitate,or palmitate in combination with CCAAT/enhancer binding protein(C/EBP)β si RNA or G0 S2 si RNA. The m RNA expression of C/EBPβ,peroxisome proliferator-activated receptor(PPAR)γ and PPARγ target genes(G0 S2,GPR81,GPR109 A and Adipoq) was examined by q PCR. The protein expression of C/EBPβ,PPARγ,and G0 S2 was determined by Western blotting. Lipid accumulation was detected with Oil Red O staining and quantified by absorbance value of the extracted Oil Red O dye. Lipolysis was evaluated by measuring the amount of glycerol released into the medium. RESULTS Palmitate caused a dose-dependent increase in lipid accumulation and a dose-dependent decrease in lipolysis in Hep G2 cells. In addition,palmitate increased the m RNA expression of C/EBPβ,PPARγ,and PPARγ target genes(G0 S2,GPR81,GPR109 A,and Adipoq) and the protein expression of C/EBPβ,PPARγ,and G0 S2 in a dose-dependent manner. Knockdown of C/EBPβ decreased palmitate-induced PPARγ and its target genes(G0 S2,GPR81,GPR109 A,and Adipoq) m RNA expression and palmitate-induced PPARγ and G0 S2 protein expression in Hep G2 cells. Knockdown of C/EBPβ also attenuated lipid accumulation and augmented lipolysis in palmitate-treated Hep G2 cells. G0 S2 knockdown attenuated lipid accumulation and augmented lipolysis,while G0 S2 knockdown had no effects on the m RNA expression of C/EBPβ,PPARγ,and PPARγ target genes(GPR81,GPR109 A and Adipoq) in palmitate-treated Hep G2 cells. CONCLUSION Palmitate can induce lipid accumulation in Hep G2 cells by activating C/EBPβ-mediated G0 S2 expression.
文摘目的:探讨脂肪相关基因(fat mass and obesity associated gene,FTO)及其抑制剂大黄酸(rhein)在非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)中的作用。方法:采用高脂饲料喂养的方法构建NAFLD小鼠模型,利用灌胃的方式使用rhein进行治疗。为评估造模是否成功及药物治疗效果,分别采用H-E染色、油红染色确定小鼠肝细胞中脂肪沉积的情况,采用Western blot检测FTO蛋白在小鼠肝脏组织中的变化情况。结果:与普饲组相比,高脂组小鼠的摄食量明显降低(P<0.01),高脂+rhein组小鼠的体质量明显低于高脂组(P<0.05)。与高脂组相比,高脂+rhein组小鼠肝细胞中脂肪空泡明显减少,高脂组小鼠肝细胞中脂肪沉积明显多于普饲组,rhein灌胃的小鼠肝细胞中脂肪沉积明显减少。与高脂组相比,高脂+rhein组小鼠的脂肪代谢明显恢复。FTO蛋白在高脂组小鼠的肝组织中显著增多,而在高脂+rhein组小鼠肝组织中FTO蛋白的表达量明显回落。结论:Rhein可减少NAFLD小鼠模型中肝组织FTO蛋白的表达,有治疗NAFLD的潜能。
文摘BACKGROUND Dyslipidemias are metabolic abnormalities associated with chronic diseases caused by genetic and environmental factors.The Mexican population displays regional differences according to ethnicity with an impact on the type of dyslipidemia.AIM To define the main dyslipidemias,the frequency of lipid-related risk alleles,and their association with hyperlipidemic states among different ethnic groups in West Mexico.METHODS In a retrospective study,1324 adults were selected to compare dyslipidemias and lipid-related gene polymorphisms.Demographic,clinical,and laboratory data were collected.A subgroup of 196 normal weight subjects without impaired glucose was selected for the association analyses.Genotyping was determined by allelic discrimination assay.RESULTS Hypercholesterolemia was the most prevalent dyslipidemia(42.3%).The frequency of the risk alleles associated with hypoalphalipoproteinemia(ABCA1)and hypercholesterolemia(APOE,LDLR)was higher in the Native Americans(P=0.047).In contrast,the Mestizos with European ancestry showed a higher frequency of the risk alleles for hypertriglyceridemia(APOE2,MTTP)(P=0.045).In normal weight Mestizo subjects,the APOB TT and LDLR GG genotypes were associated risk factors for hypercholesterolemia(OR=5.33,95%CI:1.537-18.502,P=0.008 and OR=3.90,95%CI:1.042-14.583,P=0.043,respectively),and displayed an increase in low-density lipoprotein cholesterol levels(APOB:β=40.39,95%CI:14.415-66.366,P=0.004;LDLR:β=20.77,95%CI:5.763-35.784,P=0.007).CONCLUSION Gene polymorphisms and dyslipidemias showed a differential distribution.Regional primary health care strategies are required to mitigate their prevalence considering the genetic and environmental features which could have important implications for personalized medicine within the new era of precision medicine.
