Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,memb...Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway.Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.展开更多
Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effec...Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedent...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.展开更多
Metabolic syndrome has been widely recognized in various studies as being intricately linked to the initiation and progression of colorectal adenoma. The potential pathways through which metabolic syndrome influences ...Metabolic syndrome has been widely recognized in various studies as being intricately linked to the initiation and progression of colorectal adenoma. The potential pathways through which metabolic syndrome influences colorectal adenoma encompass chronic inflammation, insulin resistance, oxidative stress, and dysbiosis of the intestinal flora. This review aims to consolidate the understanding of the association between metabolic syndrome and colorectal adenoma, elucidating the interconnected mechanisms between different metabolic syndrome-related disorders and colorectal adenoma. By shedding light on these connections, this review offers valuable insights for the preventive strategies targeting colorectal adenoma.展开更多
BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage re...BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage remains unclear.AIM To determine the role and mechanism of UGT1A1 in liver damage progression.METHODS We investigated the relationship between UGT1A1 expression and liver injury through clinical research.Additionally,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study.RESULTS Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis.This suggests that low UGT1A1 levels may be associated with the progression of liver damage.In mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be increased.In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ACLF.UGT1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid metabolism.CONCLUSION UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver injury.UGT1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.展开更多
Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19,especially those with pre-existing cardiovascular diseases(CVDs)and diabetes....Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19,especially those with pre-existing cardiovascular diseases(CVDs)and diabetes.Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province,China between December 31,2019 and April 21,2020.Patients who were aged<18 or≥85 years old,in pregnancy,with acute lethal organ injury(e.g.,acute myocardial infarction,severe acute pancreatitis,acute stroke),hypothyroidism,malignant diseases,severe malnutrition,and those with normal lipid profile under lipid-lowering medicines(e.g,statin,niacin,fenofibrate,gemfibrozil,and ezetimibe)were excluded.Propensity score matching(PSM)analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia.PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride(TG),increased low・density lipoprotein cholesterol(LDL-C),and decreased high-density lipoprotein cholesterol(HDL-C).Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters.The results were verified in male,female patients,and in patients with pre-existing CVDs and type 2 diabetes.Results Of 1094S inpatients confirmed as COVID-19,there were 9822 inpatients included in the study,comprising 3513(35.8%)cases without hyperlipidemia and 6309(64.2%)cases with hyperlipidemia.Based on a mixed-effect Cox model after PSM at 1:1 ratio,hyperlipidemia was not associated with increased or decreased 28-day all-cause death[adjusted hazard ratio(HR),1.17(95%C/,0.95-1.44),P二0.151].Wb found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality[adjusted HR,1.23(95%CI,0.98-1.55),P=0.075 in TG increase group;0.78(95%CI,0.57-1.07),P=0.123 in LDL-C increase group;and 1.12(95%CI,0.9-1.39),P=0.299 in HDL-C decrease group,respectively].Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes,and in both male and female cohorts.Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients,even in those accompanied with CVDs or diabetes.Similar results were also obtained in subgroup analyses of abnormal lipid parameters.Therefore,hyperlipidemia might be not a major causative factor for poor outcome of COVID-19,which provides guidance for the intervention of inpatients during the epidemic of COVID-19.展开更多
The current letter to the editor pertains to the manuscript entitled'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'.Increased levels of uridine diphosphate glucuronos...The current letter to the editor pertains to the manuscript entitled'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'.Increased levels of uridine diphosphate glucuronosyltransferase 1A1 during liver injury could mitigate damage by reducing endoplasmic reticulum stress,oxidative stress,and dysregulated lipid metabolism,impeding hepatocyte apoptosis and necroptosis.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to trea...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver,among which Dendrobium nobile Lindl.powder has been affirmed by many doctors and patients to be effective.However,there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.AIM To survey the effect of combining Dendrobium nobile Lindl.powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.METHODS Eighty patients with mild to moderate NAFLD participated in this retrospective study,classified into two groups:The observation group(n=40)and the control group(n=40).In November 2020 and November 2022,the study was conducted at People’s Hospital of Chongqing Liang Jiang New Area.The control group received standard treatment,while the observation group received Dendrobium nobile Lindl.powder based on the control group.The study compared differences in traditional Chinese medicine clinical syndrome scores,liver fibrosis treatment,liver function indicators,lipid levels,and serum inflammatory factor levels before and after treatment,and we calculated the incidence of adverse reactions for both groups.RESULTS The total effective rate was 97.50%in the observation group and 72.5%in the control group.After 8 weeks of treatment,the main and secondary symptom scores remarkably decreased,especially in the observation group(P<0.05),and there was a significant reduction in the serum levels of hyaluronic acid(HA),laminin(LN),human rocollagen III(PC III),and collagen type IV(CIV).The levels of HA,LN,PC III,and CIV were significantly lower in the observation group(P<0.05).After 8 weeks,both groups indicated remarkable improvements in liver function and blood lipid levels,with the observation group having even lower levels(P<0.05).Serum levels of interleukin-1β,tumor necrosis factor-α,and interleukin-8 also dropped significantly.The observation group had a lower rate of adverse reactions(5.00%)compared to the control group(22.50%).CONCLUSION Adding Dendrobium nobile Lindl.powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease.It also enhances hepatic function and lipid profile,ameliorates liver fibrosis indices,and lowers the risk of side effects.Consequently,this therapeutic protocol shows promise for clinical implementation and dissemination.展开更多
The goal this review is to clarify the effects of the fat mass and obesity-associated protein (FTO) in lipid metabolism regulation and related underlying mechanisms through the FTO-mediated demethylation of m6A modifi...The goal this review is to clarify the effects of the fat mass and obesity-associated protein (FTO) in lipid metabolism regulation and related underlying mechanisms through the FTO-mediated demethylation of m6A modification. FTO catalyzes the demethylation of m6A to alter the processing, maturation and translation of the mRNAs of lipid-related genes. FTO overexpression in the liver promotes lipogenesis and lipid droplet (LD) enlargement and suppresses CPT-1–mediated fatty acid oxidation via the SREBP1c pathway, promoting excessive lipid storage and nonalcoholic fatty liver diseases (NAFLD). FTO enhances preadipocyte differentiation through the C/EBPβ pathway, and facilitates adipogenesis and fat deposition by altering the alternative splicing of RUNX1T1, the expression of PPARγ and ANGPTL4, and the phosphorylation of PLIN1, whereas it inhibits lipolysis by inhibiting IRX3 expression and the leptin pathway, causing the occurrence and development of obesity. Suppression of the PPARβ/δ and AMPK pathways by FTO-mediated m6A demethylation damages lipid utilization in skeletal muscles, leading to the occurrence of diabetic hyperlipidemia. m6A demethylation by FTO inhibits macrophage lipid influx by downregulating PPARγ protein expression and accelerates cholesterol efflux by phosphorylating AMPK, thereby impeding foam cell formation and atherosclerosis development. In summary, FTO-mediated m6A demethylation modulates the expression of lipid-related genes to regulate lipid metabolism and lipid disorder diseases.展开更多
Background There is a paucity of data about the best lipid ratio predicting the severity of coronary artery disease （CAD） in patients with diabetes mellitus. We determined the relationship between five conventional ...Background There is a paucity of data about the best lipid ratio predicting the severity of coronary artery disease （CAD） in patients with diabetes mellitus. We determined the relationship between five conventional lipid ratios and the extent of coronary artery lesions in Chinese Type 2 diabetics with stable angina pectoris （SAP）. Methods A prospective cohort study within 373 type 2 diabetic patients diag- nosed with stable CAD by coronary angiography was performed. All patients were classified into three groups according to the tertiles of Gensini scores （GS, low group 〈 8 points n = 143; intermediate group 8-28 points, n = 109; high group 〉 28 points, n = 121）. Association between the ratios of apolipoprotein （apo） B and apoA-1, total cholesterol and high density lipoprotein cholesterol （TC/HDL-C）, triglycerides and HDL-C （TG/HDL-C）, low density lipoprotein cholesterol and HDL-C （LDL-C/HDL-C）, Non-HDL-C/HDL-C and GS were evaluated using the receivers operating characteristic （ROC） curves and multivariate logistic regression models. Results The ratio of apoB/apoA-1, TC/HDL-C, LDL-C/HDL-C, and Non-HDL-C/HDL-C were correlated with Gensini scores. Area under the ROC curves for predicting high Gensini scores in the ratios of apoB/apoA-1, TC/HDL-C, LDL-C/HDL-C and Non-HDL-C/HDL-C were 0.62, 0.60, 0.59 and 0.60, respec- tively （P 〈 0.005 for all）. According to multivariate logistic regression analysis after adjusted with demographic characteristic and other lipid parameters, the ratio of apoB/apoA-1 is qualified as an independent discriminator for the severity of CAD. However, after fiu-ther adjusting different baseline variables, such as left ventricular ejective fraction, hemoglobin Alc, leukocytes count and serum creatinine, none of the above lipid ratios remained. Conclusions Compared with other lipid parameters, the ratio of apoB/apoA-1 appears to be more significantly correlated with the extent of coronary artery lesions in Chinese diabetics, but it was not an independent predictor in these settings.展开更多
The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes.Progestin and adipoQ receptor 3(PAQR3),a key regulator of inflammation and metabolism,can negatively regulate the ...The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes.Progestin and adipoQ receptor 3(PAQR3),a key regulator of inflammation and metabolism,can negatively regulate the PI3 K/AKT signaling pathway.Here,we report that gentiopicroside(GPS),the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa,decreased lipid synthesis and increased glucose utilization in palmitic acid(PA) treated HepG2 cells.Additionally,GPS improved glycolipid metabolism in streptozotocin(STZ) treated high-fat diet(HFD)-induced diabetic mice.Our findings revealed that GPS promoted the activation of the PI3 K/AKT axis by facilitating DNA-binding protein 2(DDB2)-mediated PAQR3 ubiquitinated degradation.Moreover,results of surface plasmon resonance(SPR),microscale thermophoresis(MST) and thermal shift assay(TSA) indicated that GPS directly binds to PAQR3.Results of molecular docking and cellular thermal shift assay(CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH2-terminus including Leu40,Asp42,Glu69,Tyr125 and Ser129,and spatially inhibited the interaction between PAQR3 and the PI3 K catalytic subunit(P110α) to restore the PI3 K/AKT signaling pathway.In summary,our study identified GPS,which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway,as a potential drug candidate for the treatment of diabetes.展开更多
Type 2 diabetes mellitus(T2DM)is a burdensome global disease.In-depth understanding of its mechanism will help to optimize diagnosis and treatment,which reduces the burden.Multi-omics research has unparalleled advanta...Type 2 diabetes mellitus(T2DM)is a burdensome global disease.In-depth understanding of its mechanism will help to optimize diagnosis and treatment,which reduces the burden.Multi-omics research has unparalleled advantages in contributing to the overall understanding of the mechanism of this chronic metabolic disease.In the past two decades,the study of multi-omics on T2DMrelated intestinal flora perturbation and plasma dyslipidemia has shown tremendous potential and is expected to achieve major breakthroughs.The regulation of intestinal flora in diabetic patients has been confirmed by multiple studies.The use of metagenomics,16S RNA sequencing,and metabolomics has comprehensively identified the overall changes in the intestinal flora and the metabolic disturbances that could directly or indirectly participate in the intestinal flora-host interactions.Lipidomics combined with other“omics”has characterized lipid metabolism disorders in T2DM.The combined application and crossvalidation of multi-omics can screen for dysregulation in T2DM,which will provide immense opportunities to understand the mechanisms behind T2DM.展开更多
Objective： To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyo- pathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. Methods： ...Objective： To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyo- pathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. Methods： Sixty Sprague-Dawley （SD） rats were randomly divided into six groups： a normal control group （NC）, an obesity group （OB）, a diabetic cardiomyopathy group （DCM）, a tea polyphenol group （TP）, an obesity tea polyphenol treatment group （OB-TP）, and a diabetic cardiomyopathy tea polyphenol treatment group （DCM-TP）. After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ul- trasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-11, SQSTM1/p62, and Beclin-1 were determined by Western blotting. Results： Com- pared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-11/I and Beclin-1 increased obviously whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups （P〈0.05）. Conclusions： Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.展开更多
EGb761,a standardized and well-defined product extract of Ginkgo biloba leaves,has beneficial effects on the treatment of multiple diseases,including diabetes and dyslipidemia.However,it is still unclear whether EGb76...EGb761,a standardized and well-defined product extract of Ginkgo biloba leaves,has beneficial effects on the treatment of multiple diseases,including diabetes and dyslipidemia.However,it is still unclear whether EGb761 can increase insulin sensitivity.The objectives of the present study are to evaluate the effects of EGb761 on insulin sensitivity in an obese and insulinresistant mouse model,established through chronic feeding of C57BL/6J mice with a high-fat diet(HFD),and to explore potential mechanisms.Mice fed with HFD for 18 weeks(starting from 4 weeks of age)developed obesity,dyslipidemia(as indicated by biochemical measurements of blood glucose,triglyceride(TG),total cholesterol(TC),and free fatty acids(FFA)),and insulin resistance(as determined by the oral glucose tolerance test(OGTT)and the homeostasis model assessment of insulin resistance(HOMA-IR)index),compared to control mice fed with a standard laboratory chow.Oral treatment of the HFD-fed mice with EGb761,at low(100 mg/kg),medium(200 mg/kg),or high(400 mg/kg)doses,via oral gavage(once daily)for 8 weeks(starting from 26 weeks of age)dose-dependently enhanced glucose tolerance in OGTT,and decreased both the insulin levels(by 29%,55%,and 70%,respectively),and the HOMA-IR index values(by 50%,69%,and 80%,respectively).EGb761 treatment also ameliorated HFD-induced obesity,dyslipidemia,and liver injury,as indicated by decreases in body weight(by 4%,11%,and 16%,respectively),blood TC levels(by 23%,32%,and 37%,respectively),blood TG levels(by 17%,23%,and 33%,respectively),blood FAA levels(by 35%,38%,and 46%,respectively),and liver index(liver weight/body weight)values(by 12.8%,25%,and 28%,respectively)in the low,medium,and high EGb761 dose groups,respectively.In further mechanism studies,EGb761 was found to protect hepatic insulin receptor b and insulin receptor substrate 1 from HFD-induced degradation,and to keep the AMP-activated protein kinase,which plays a crucial role in reducing lipotoxicity,from HFD-induced inactivation.We conclude that EGb761 can effectively reduce HFD-induced insulin resistance and ameliorate other symptoms of the metabolic syndrome.展开更多
基金supported by the Natural Science Research Project of colleges and Universities in Anhui Province[2022AH052336]High Level Talent Research Initiation Fund Of Anhui Medical College[2023RC004]。
文摘Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway.Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.
基金supported by the grants from National Natural Science Foundation of China(No.82174334)Hainan Provincial Key Laboratory of Tropical Brain Science Research and Transformation Research Project(JCKF2021001)Innovative Research Projects for Graduate Students(HYYS2021B01).
文摘Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.
基金the Scientific Research Project of Jiangsu Health Commission,No.Z2022078the Natural Science Foundation of Jiangsu Province,No.BK20220299.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.
文摘Metabolic syndrome has been widely recognized in various studies as being intricately linked to the initiation and progression of colorectal adenoma. The potential pathways through which metabolic syndrome influences colorectal adenoma encompass chronic inflammation, insulin resistance, oxidative stress, and dysbiosis of the intestinal flora. This review aims to consolidate the understanding of the association between metabolic syndrome and colorectal adenoma, elucidating the interconnected mechanisms between different metabolic syndrome-related disorders and colorectal adenoma. By shedding light on these connections, this review offers valuable insights for the preventive strategies targeting colorectal adenoma.
基金the Science and Technology Research Foundations of Guizhou Province,No.QKHJC-ZK(2022)YB642Zunyi Science and Technology Plan Project,No.ZSKHHZ(2022)344,No.ZSKHHZ(2022)360,and No.ZYK160+2 种基金Hubei Province Central Leading Local Science and Technology Development Special Project,No.2022BCE030Changzhou Science and Technology Projects,No.CE20225054Bijie City Science and Planning Bureau,No.BKH(2022)8.
文摘BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage remains unclear.AIM To determine the role and mechanism of UGT1A1 in liver damage progression.METHODS We investigated the relationship between UGT1A1 expression and liver injury through clinical research.Additionally,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study.RESULTS Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis.This suggests that low UGT1A1 levels may be associated with the progression of liver damage.In mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be increased.In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ACLF.UGT1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid metabolism.CONCLUSION UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver injury.UGT1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.
基金National Key R&D Program of China(2016YFF0101500)the National Natural Science Foundation of China(81970364,81770053).
文摘Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19,especially those with pre-existing cardiovascular diseases(CVDs)and diabetes.Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province,China between December 31,2019 and April 21,2020.Patients who were aged<18 or≥85 years old,in pregnancy,with acute lethal organ injury(e.g.,acute myocardial infarction,severe acute pancreatitis,acute stroke),hypothyroidism,malignant diseases,severe malnutrition,and those with normal lipid profile under lipid-lowering medicines(e.g,statin,niacin,fenofibrate,gemfibrozil,and ezetimibe)were excluded.Propensity score matching(PSM)analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia.PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride(TG),increased low・density lipoprotein cholesterol(LDL-C),and decreased high-density lipoprotein cholesterol(HDL-C).Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters.The results were verified in male,female patients,and in patients with pre-existing CVDs and type 2 diabetes.Results Of 1094S inpatients confirmed as COVID-19,there were 9822 inpatients included in the study,comprising 3513(35.8%)cases without hyperlipidemia and 6309(64.2%)cases with hyperlipidemia.Based on a mixed-effect Cox model after PSM at 1:1 ratio,hyperlipidemia was not associated with increased or decreased 28-day all-cause death[adjusted hazard ratio(HR),1.17(95%C/,0.95-1.44),P二0.151].Wb found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality[adjusted HR,1.23(95%CI,0.98-1.55),P=0.075 in TG increase group;0.78(95%CI,0.57-1.07),P=0.123 in LDL-C increase group;and 1.12(95%CI,0.9-1.39),P=0.299 in HDL-C decrease group,respectively].Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes,and in both male and female cohorts.Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients,even in those accompanied with CVDs or diabetes.Similar results were also obtained in subgroup analyses of abnormal lipid parameters.Therefore,hyperlipidemia might be not a major causative factor for poor outcome of COVID-19,which provides guidance for the intervention of inpatients during the epidemic of COVID-19.
文摘The current letter to the editor pertains to the manuscript entitled'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'.Increased levels of uridine diphosphate glucuronosyltransferase 1A1 during liver injury could mitigate damage by reducing endoplasmic reticulum stress,oxidative stress,and dysregulated lipid metabolism,impeding hepatocyte apoptosis and necroptosis.
基金Supported by the Chongqing Science and Health Joint Medical Research Project,No.2022MSXM133the First Batch of Key Disciplines on Public Health in Chongqing,Natural Science Foundation of Chongqing,No.CSTB2022NSCQ-MSX1522.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver,among which Dendrobium nobile Lindl.powder has been affirmed by many doctors and patients to be effective.However,there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.AIM To survey the effect of combining Dendrobium nobile Lindl.powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.METHODS Eighty patients with mild to moderate NAFLD participated in this retrospective study,classified into two groups:The observation group(n=40)and the control group(n=40).In November 2020 and November 2022,the study was conducted at People’s Hospital of Chongqing Liang Jiang New Area.The control group received standard treatment,while the observation group received Dendrobium nobile Lindl.powder based on the control group.The study compared differences in traditional Chinese medicine clinical syndrome scores,liver fibrosis treatment,liver function indicators,lipid levels,and serum inflammatory factor levels before and after treatment,and we calculated the incidence of adverse reactions for both groups.RESULTS The total effective rate was 97.50%in the observation group and 72.5%in the control group.After 8 weeks of treatment,the main and secondary symptom scores remarkably decreased,especially in the observation group(P<0.05),and there was a significant reduction in the serum levels of hyaluronic acid(HA),laminin(LN),human rocollagen III(PC III),and collagen type IV(CIV).The levels of HA,LN,PC III,and CIV were significantly lower in the observation group(P<0.05).After 8 weeks,both groups indicated remarkable improvements in liver function and blood lipid levels,with the observation group having even lower levels(P<0.05).Serum levels of interleukin-1β,tumor necrosis factor-α,and interleukin-8 also dropped significantly.The observation group had a lower rate of adverse reactions(5.00%)compared to the control group(22.50%).CONCLUSION Adding Dendrobium nobile Lindl.powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease.It also enhances hepatic function and lipid profile,ameliorates liver fibrosis indices,and lowers the risk of side effects.Consequently,this therapeutic protocol shows promise for clinical implementation and dissemination.
基金The authors gratefully acknowledge the financial supports from the National Natural Science Foundation of China (No. 81770460)the Natural Science Foundation of Guangxi Zhuang Autonomous Region, China (No. 2019JJA140728)+3 种基金the Natural Science Foundation of Hunan Province, China (No. 2020JJ4532)Scientific Research Foundation for the Excellent Youth of the Education Department of Hunan province, China (No. 18B264)Aid Program (No. 2017KJ268)Key Lab for Clinical Anatomy & Reproductive Medicine, China (No. 2017KJ182) from the Science and Technology Bureau of Hengyang City, China.
文摘The goal this review is to clarify the effects of the fat mass and obesity-associated protein (FTO) in lipid metabolism regulation and related underlying mechanisms through the FTO-mediated demethylation of m6A modification. FTO catalyzes the demethylation of m6A to alter the processing, maturation and translation of the mRNAs of lipid-related genes. FTO overexpression in the liver promotes lipogenesis and lipid droplet (LD) enlargement and suppresses CPT-1–mediated fatty acid oxidation via the SREBP1c pathway, promoting excessive lipid storage and nonalcoholic fatty liver diseases (NAFLD). FTO enhances preadipocyte differentiation through the C/EBPβ pathway, and facilitates adipogenesis and fat deposition by altering the alternative splicing of RUNX1T1, the expression of PPARγ and ANGPTL4, and the phosphorylation of PLIN1, whereas it inhibits lipolysis by inhibiting IRX3 expression and the leptin pathway, causing the occurrence and development of obesity. Suppression of the PPARβ/δ and AMPK pathways by FTO-mediated m6A demethylation damages lipid utilization in skeletal muscles, leading to the occurrence of diabetic hyperlipidemia. m6A demethylation by FTO inhibits macrophage lipid influx by downregulating PPARγ protein expression and accelerates cholesterol efflux by phosphorylating AMPK, thereby impeding foam cell formation and atherosclerosis development. In summary, FTO-mediated m6A demethylation modulates the expression of lipid-related genes to regulate lipid metabolism and lipid disorder diseases.
文摘Background There is a paucity of data about the best lipid ratio predicting the severity of coronary artery disease （CAD） in patients with diabetes mellitus. We determined the relationship between five conventional lipid ratios and the extent of coronary artery lesions in Chinese Type 2 diabetics with stable angina pectoris （SAP）. Methods A prospective cohort study within 373 type 2 diabetic patients diag- nosed with stable CAD by coronary angiography was performed. All patients were classified into three groups according to the tertiles of Gensini scores （GS, low group 〈 8 points n = 143; intermediate group 8-28 points, n = 109; high group 〉 28 points, n = 121）. Association between the ratios of apolipoprotein （apo） B and apoA-1, total cholesterol and high density lipoprotein cholesterol （TC/HDL-C）, triglycerides and HDL-C （TG/HDL-C）, low density lipoprotein cholesterol and HDL-C （LDL-C/HDL-C）, Non-HDL-C/HDL-C and GS were evaluated using the receivers operating characteristic （ROC） curves and multivariate logistic regression models. Results The ratio of apoB/apoA-1, TC/HDL-C, LDL-C/HDL-C, and Non-HDL-C/HDL-C were correlated with Gensini scores. Area under the ROC curves for predicting high Gensini scores in the ratios of apoB/apoA-1, TC/HDL-C, LDL-C/HDL-C and Non-HDL-C/HDL-C were 0.62, 0.60, 0.59 and 0.60, respec- tively （P 〈 0.005 for all）. According to multivariate logistic regression analysis after adjusted with demographic characteristic and other lipid parameters, the ratio of apoB/apoA-1 is qualified as an independent discriminator for the severity of CAD. However, after fiu-ther adjusting different baseline variables, such as left ventricular ejective fraction, hemoglobin Alc, leukocytes count and serum creatinine, none of the above lipid ratios remained. Conclusions Compared with other lipid parameters, the ratio of apoB/apoA-1 appears to be more significantly correlated with the extent of coronary artery lesions in Chinese diabetics, but it was not an independent predictor in these settings.
基金supported by research grants from the National Natural Science Foundation of China (No.81770816 and 81973375)the Key Project of Natural Science Foundation of Guangdong Province,China (No.2017A030311036)+1 种基金Seed Program of Guangdong Province (No.2017B090903004,China)Guangdong Provincial Key Field and Program Project (No.2020B1111100004,China)。
文摘The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes.Progestin and adipoQ receptor 3(PAQR3),a key regulator of inflammation and metabolism,can negatively regulate the PI3 K/AKT signaling pathway.Here,we report that gentiopicroside(GPS),the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa,decreased lipid synthesis and increased glucose utilization in palmitic acid(PA) treated HepG2 cells.Additionally,GPS improved glycolipid metabolism in streptozotocin(STZ) treated high-fat diet(HFD)-induced diabetic mice.Our findings revealed that GPS promoted the activation of the PI3 K/AKT axis by facilitating DNA-binding protein 2(DDB2)-mediated PAQR3 ubiquitinated degradation.Moreover,results of surface plasmon resonance(SPR),microscale thermophoresis(MST) and thermal shift assay(TSA) indicated that GPS directly binds to PAQR3.Results of molecular docking and cellular thermal shift assay(CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH2-terminus including Leu40,Asp42,Glu69,Tyr125 and Ser129,and spatially inhibited the interaction between PAQR3 and the PI3 K catalytic subunit(P110α) to restore the PI3 K/AKT signaling pathway.In summary,our study identified GPS,which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway,as a potential drug candidate for the treatment of diabetes.
基金Supported by Grant from International Joint Usage/Research Center,the Institute of Medical Science,the University of Tokyo,No.New-2020-K2012and Open Project of Shandong Provincial Key Laboratory of Infection and Immunity,No.2.
文摘Type 2 diabetes mellitus(T2DM)is a burdensome global disease.In-depth understanding of its mechanism will help to optimize diagnosis and treatment,which reduces the burden.Multi-omics research has unparalleled advantages in contributing to the overall understanding of the mechanism of this chronic metabolic disease.In the past two decades,the study of multi-omics on T2DMrelated intestinal flora perturbation and plasma dyslipidemia has shown tremendous potential and is expected to achieve major breakthroughs.The regulation of intestinal flora in diabetic patients has been confirmed by multiple studies.The use of metagenomics,16S RNA sequencing,and metabolomics has comprehensively identified the overall changes in the intestinal flora and the metabolic disturbances that could directly or indirectly participate in the intestinal flora-host interactions.Lipidomics combined with other“omics”has characterized lipid metabolism disorders in T2DM.The combined application and crossvalidation of multi-omics can screen for dysregulation in T2DM,which will provide immense opportunities to understand the mechanisms behind T2DM.
基金Project supported by the Scientific and Technological Projects for Medicine and Health of Zhejiang Province(No.2015128660)the Major Research and Development Projects for the Zhejiang Science and Technology Agency(No.2017C03034),China
文摘Objective： To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyo- pathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. Methods： Sixty Sprague-Dawley （SD） rats were randomly divided into six groups： a normal control group （NC）, an obesity group （OB）, a diabetic cardiomyopathy group （DCM）, a tea polyphenol group （TP）, an obesity tea polyphenol treatment group （OB-TP）, and a diabetic cardiomyopathy tea polyphenol treatment group （DCM-TP）. After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ul- trasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-11, SQSTM1/p62, and Beclin-1 were determined by Western blotting. Results： Com- pared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-11/I and Beclin-1 increased obviously whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups （P〈0.05）. Conclusions： Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.
基金supported by the National S&T Major Project(Nos.2009ZX09103-432 and 2009ZX09301-003-12-1)Natural Sciences Funds of Inner Mongolian Autonomous Region(No.20080404Zd31)。
文摘EGb761,a standardized and well-defined product extract of Ginkgo biloba leaves,has beneficial effects on the treatment of multiple diseases,including diabetes and dyslipidemia.However,it is still unclear whether EGb761 can increase insulin sensitivity.The objectives of the present study are to evaluate the effects of EGb761 on insulin sensitivity in an obese and insulinresistant mouse model,established through chronic feeding of C57BL/6J mice with a high-fat diet(HFD),and to explore potential mechanisms.Mice fed with HFD for 18 weeks(starting from 4 weeks of age)developed obesity,dyslipidemia(as indicated by biochemical measurements of blood glucose,triglyceride(TG),total cholesterol(TC),and free fatty acids(FFA)),and insulin resistance(as determined by the oral glucose tolerance test(OGTT)and the homeostasis model assessment of insulin resistance(HOMA-IR)index),compared to control mice fed with a standard laboratory chow.Oral treatment of the HFD-fed mice with EGb761,at low(100 mg/kg),medium(200 mg/kg),or high(400 mg/kg)doses,via oral gavage(once daily)for 8 weeks(starting from 26 weeks of age)dose-dependently enhanced glucose tolerance in OGTT,and decreased both the insulin levels(by 29%,55%,and 70%,respectively),and the HOMA-IR index values(by 50%,69%,and 80%,respectively).EGb761 treatment also ameliorated HFD-induced obesity,dyslipidemia,and liver injury,as indicated by decreases in body weight(by 4%,11%,and 16%,respectively),blood TC levels(by 23%,32%,and 37%,respectively),blood TG levels(by 17%,23%,and 33%,respectively),blood FAA levels(by 35%,38%,and 46%,respectively),and liver index(liver weight/body weight)values(by 12.8%,25%,and 28%,respectively)in the low,medium,and high EGb761 dose groups,respectively.In further mechanism studies,EGb761 was found to protect hepatic insulin receptor b and insulin receptor substrate 1 from HFD-induced degradation,and to keep the AMP-activated protein kinase,which plays a crucial role in reducing lipotoxicity,from HFD-induced inactivation.We conclude that EGb761 can effectively reduce HFD-induced insulin resistance and ameliorate other symptoms of the metabolic syndrome.
