ABSTRACT
Objective To investigate he intervention effect of knockdown of activating transcription factor 4(ATF-4)on fructose-induced lipid accumulation in liver cells. Methods HepG2 cells were divided into the control group(C),high fructose group(F),high-fructose+negative control group(F+NC)and high-fructose+ATF-4 siRNA group(F+ATF-4-). The mRNA level of gens of the upstream transcriptional factors and ERS markers was detected. The protein level of ACC,FAS and SCD-1 was also detected. Results Compared with group C,the mRNA expression of SREBP-1c,ChREBP,GRP78 and CHOP was increased(P < 0.01),while ATF-4 knock-down decreased the expression of the above genes(P < 0.01 ,respectively). Compared with group C ,the protein expression of ACC,FAS and SCD-1 was increased in group F(P<0.01,respectively). While ATF-4 knockdown decreased the protein expression of ACC ,FAS and SCD-1. Conclusions ATF-4 knockdown can improve the lipid steatosis induced by fructose through down-regulating lipid lipogenesis ,indicating ATF-4 possesses a regulatory effect on lipogenesis.
ABSTRACT
Objective To observe the effect of fenofibrate intervention on high-fructose-feeding-induced liver steatosis in rats and explore the possible mechanism. Methods Male Wistar rats were randomly divided into control group ,high fructose group and fenofibrate group[fenofibrate intervention started after 8 weeks of high fructose feeding ,30 mg/(kg · d)]. Rats were sacrificed after 12-week of high fructose feeding. Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),free triglyceride(TG)and liver TG content were determined;protein levels of fatty acid synthase(FAS),endoplasmic reticulum stress mark-er Bip and autophagy markers such as Atg7,Beclin1,LC3 and the related pathway mTOR in liver tissues were de-tected. Results Compared with those in control group and fenofibrate group,serum AST,serum total cholesterol, blood free TG and hepatic TG were significantly increased in high-fructose group(P < 0.01). The protein expres-sion of Fas,Bip and mTOR were significantly increased in high-fructose group compared with those in control group and fenofibrate group;the protein expression of Atg7,beclin1 and LC3 were significantly decreased in high-fructose group compared with those in control group and fenofibrate group. Conclusions Long-term high-fructose-feeding induces fatty liver and liver cell injury ,and may affect ERS and autophagy. High-fructose-feeding-in-duced fatty liver may be improved by fenofibrate and its underlying mechanism might be associated with Fas,ERS and autophagy in liver.
ABSTRACT
[Summary] Activating transcription factor 4 (ATF4) is an alkaline leucine zipper transcriptional factor ,which is involved in many physiological metabolism processes such as stress response ,inflammation and tumor growth. Moreover ,recent studies have shown that ATF4 also plays a key role in regulating lipid and glucose metabolism ,insulin secretion and insulin sensitivity ,which may related to pathways such as endoplasmic reticulum stress (ERS ) ,peroxisome proliferator‐activated receptor gamma coactivator (PGC1α) and target of rapamycin (TOR). This article summarized the recent research progress of ATF4 in regulating glucose and lipid metabolism.
ABSTRACT
Objective To explore the impact of high-fat diet on bone marrow-originated endothelial progenitor cells(EPCs),oxidative stress and glutathione peroxidase-1 (GPx-1) expression in rats.Methods 23 male Wistar rats were randomly divided into normal control group (NC goup,n=13) and high-fat fed group (HF group,n=10).Rats in NC group were fed with a standard lab diet,and rats in HF group were fed with a high-fat diet (502 kcal/100 g).Lee's index,body weight were measured to evaluate whether the obese rat model was established at 16 weeks after feeding.Blood samples were collected via carotid arterial cannula.Serum insulin,lipids and oxidative stress index were measured.Perirenal and epididymis adipose tissues were obtained and weighed.EPCs were detached,cultivated and evaluated by multi-wave laser confocal microscopy.Protein and gene expressions of GPx-1 were determined by Western blot and reverse transcription real time polymerase chain reaction(RT real-time PCR).Results After 16 weeks of high-fat diet,the body weight,Lee's index and visceral adipose tissue were increased in HF group as compared with NC group [(465.11 ±27.69) gvs.(404.38±17.01) g,(312.08±9.82) vs.(297.74±8.75),(20.07±1.94) g vs.(5.31±1.11) g,all P＜0.001].The levels of fasting blood glucose,cholesterol,triglyceride were increased in HE group as compared with NC group[(5.85±0.77) mmol/L vs.(4.285±0.74)mmol/L,(1.35±0.21) mmol/L vs.(0.95±0.14) mmol/L,(1.02±0.21) mmol/L vs.(0.65±0.19)mmol/L,all P＜0.01].The levels of fasting insulin(FIns)and HOMA-IR were higher in HF group than in NCgroup [(3.46±0.77) mmol/L vs.(2.04±0.51) mmol/L,(0.90±0.24) vs.(0.40±0.19),both P＜0.001].Levels of serum glutathion peroxidase(GSH-Px)and erythrocuprein SOD,and total anti-oxidative capacity were decreased in HF group as compared with NC group [(759.13 ±60.71) mU/L vs.(826.26±65.83) mU/L,(72.76±5.41)mU/L vs.(80.44±7.91) mU/L,(5.18±0.35) mU/L vs.(6.01±0.93) mU/L,all P＜0.05].Malonaldehyde (MDA) level was increased,EPCs count and protein and mRNA expressions of GPx-1 were decreased in HF group as compared withNC group [(6.09±0.96) mol/L vs.(5.14±0.89) μmol/L,(62.55 ± 4.85) vs.(71.19±5.95),(0.50±0.13) vs.(1.29±0.42),(0.50±0.13) vs.(1.29±0.42),all P＜0.05 or 0.01].Multiple linear regression analysis showed that MDA was an influential factor for EPCs,Lee's index was an influential factor for GSH-Px,total cholesterol (TC) was an influential factor for TAO-C and SOD,and FINs was an influential factor for MDA.Conclusions High-fat diet can induce obesity and insulin resistance,increase the visceral adiposity,decrease the quantity of EPCs and protein and mRNA expressions of GPx-1 in rats.Oxidative stress is one of influential factors for the decrease of EPCs quantity in high fat diet induced obese rats.
ABSTRACT
Objective To observe the effects of high-fat diet on liver steatosis and liver endoplasm reticulum stress in mice and to investigate the interventional effect of metfomin on them.Methods Forth-five male C57BL/J6 mice were divided into healthy control group,high-fat group and metformin group.High fat group and metformin group were fed with high-fat diet.Mice in metformin group were given metformin since the fourth week of high-fat feeding.After feeding for eight weeks,subperitoneal glucose tolerance test was performed in mice.After mice were sacrificed,liver triglyceride (TG) content and the expression of endoplasmic reticulum stress related factors at gene and protein levels were measured.One-way ANOVA was applied for analysis between groups.Results Compared with healthy control group,area under curve (AUC) of glucose tolerance and TG contents in liver tissues significantly increased in high-fat group [998±87 vs 1409±106,(10.05±0.29) μmol/g vs (27.11 ±4.76) μmol/g].Glucose tolerance and liver steatosis were improved in metformin group,AUC and TG of metformin group were significantly lower than those of high-fat group in metformin group [1178±90,(15.12±2.11) μmol/g,F=55.328,89.212,both P ＜0.01].Compared with healthy control group,the expression of glucose-regulated protein 94 (GRP94)at mRNA level significantly increased in high-fat group.Meanwhile,the expression of phosphorylated eukaryotic translation initiation factor 2α at protein level,which indicated endoplasmic reticulum stress,significantly increased.However,the expression of those endoplasmic reticulum stress markers at mRNA and protein level of metformin group were both lower than those of high fat group (F=84.002,137.321,both P＜0.05).Conclusions High fat diet caused liver steatosis in mice and accompanied by endoplasmic reticulum stress.Fatty liver was significantly improved by metformin treatment in high-fat-fed mice.The mechanism may be related with the improvement of endoplasmic reticulum stress by metformin.
ABSTRACT
The effect of oxymatrine on high-fructose-feeding induced insulin resistance and liver steatosis in rats was observed and the underlying mechanism in improving the hepatic lipid metabolism was explored.The results demonstrated that high fructose feeding decreased the glucose tolerance and increased hepatic lipid accumulation in rats,while oxymatrine could improve glucose tolerance and alleviate hepatic steatosis in rats.High fructose feeding stimulated the protein expressions of key lipid-synthesis enzymes,which were decreased by oxymatrine intervention.Both high fructose feeding and oxymatrine intervention had no significant effect on protein expressions of mitochondrial fatty acid oxidation enzymes.
ABSTRACT
Objective To explore and compare the mechanism of high-fructose and high-fat diet induced triglyceride excessive accumulation in mice liver and its relationship with endoplasmic reticulum (ER) stress.Methods 45 Adult male C57BL/J6 mice,weight arranged from 25 gram to 30 gram were randomly divided into control group,high-fructose group and high-fat group,15 mice in each group.Common food was fed in control group,high-fructose food was fed in high-fructose group,high-fat food was fed in high-fat group,and the everyday calories consumption in 3 groups was almost equal.Intraperitoneal glucose tolerance test (ipGTT) was performed after feeding for 8 weeks.After mice were sacrificed,triglyceride content,lipogenic enzymes and ER stress markers expression in liver tissues of each group were measured.Results After feeding with different food for 8 weeks,the fat content of epididymis in high-fructose group and high-fat group both was (2.0±0.1) g/100 g (body weight),which was significantly higher than that of control group (1.2 ± 0.1) g/100 g (body weight),P＜0.01).After ipGTT test,the area under curve of blood glucose in high-fructose group and high-fat group was significantly higher than that in control group (P＜0.01).Compared with control group,triglyceride contents of liver tissues in high-fructose group and high-fat group were significantly increased,of those triglyceride contents in high-fructose group increased more obviously,and triglyceride contents in high-fructose group was significantly higher than that of high-fat group (P＜0.01).Compared with control group,the expression of acylCoA carboxylase (ACC),fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1) increased in high-fructose group (P＜0.01),while decreased in high-fat group (P＜0.05) ; meanwhile,the expression of phosphorylated pancreatic ER kinase (p-PERK),inositol requiring enzyme 1 (p-IRE-1/t-IRE-1)and glucose-regulated protein 78 (GRP78) was up-regulated in both high-fructose group and high-fat group (all P＜0.01).Conclusion Both high-fructose diet and high-fat diet can induce fatty liver through different mechanisms.High-frucose diet promotes endogenous lipogenesis while high-fat diet inhibits endogenous lipogenesis.Both dietary factors can induce ER stress,which indicate that ER stress is associated with pathogenesis and development of food factors induced fatty liver.
ABSTRACT
Plasma VEGF level of T2DM was higher than that of normal control （NC, n=30） and progressively increases from normal albuminuria （NA, n=26） to microalbuminuria （MA,n=26） and to macroalbu-minuria （ODN, n=24） groups, The VEGF level was positively correlated with the levels of creatinine, HbA1c and UAER and, decreases after losartan treatment in groups of MA and ODN.
ABSTRACT
Bioeleotrical activities of human cerebral cortex which control and regalate movements get to increase during voluntary movements, the metabolic level of the cells of motor areas change at the same time,and consequently regiond cerebrd blood flow (rCBF)changes. Different changes of rCBF indicate the range of motor areas with which the relavant movemats are involved.And studies of this take great significance in finding out the basic active regalarity and features of human brain. In this artide motheds of the determination of rCBF an introduced briefly, and changes and distribution of rCBF of rCBF of each cortical moter area during different types of volantary movements are discribed.