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Objective To investigate the ameliorative effect of Lentinan (LNT) on sodium arsenite (SA)-induced hepatic lipid deposition in mice. Methods C57BL/6 mice were used as the experimental subjects, which were divided into control group, SA-exposed group, LNT + SA-exposed group and LNT control group. Blood and liver tissue samples were collected at the end of the experiment, and serum glutathione transaminase (ALT) and glutathione aminotransferase (AST) levels were detected by enzyme-linked immunosorbent assay (ELISA). A part of liver tissues was stained with hematoxylin-eosin (HE) or oil red O to observe the characteristics of liver pathological damage and lipid deposition, and another part of liver tissues was used to detect triglyceride (TG) and Adiponectin (APN) levels by ELISA. Results Compared with control group or LNT control group, SA-exposed group showed the increased levels of AST and ALT, showing the characteristics of liver histopathological damage and lipid deposition, and the APN level decreased while the TG level increased (P<0.05). Compared with SA-exposed group, the levels of AST and ALT decreased in LNT + SA-exposed group, showing the reduced degree of liver tissue damage and lipid deposition, and APN level upregulated while TG level downregulated (P<0.05). Conclusion Chronic SA exposure induces liver function damage, APN downregulation and lipid deposition in C57BL/6 mice, while LNT intervention leads to the significantly improvement of hepatic damage and lipid deposition, which may be related to the elevated APN level in liver.
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Hepatic lipid deposition is one of the basic manifestations of obesity, and nowadays pharmacological treatment is the most important tool. Punicalagin(PU), a polyphenol derived from pomegranate peel, is a potential anti-obesity substance. In this study, 60 C57BL/6J mice were randomly divided into a normal group and a model group. After establishing a model of simple obesity with a high-fat diet for 12 weeks, the successfully established rat models of obesity were then regrouped into a model group, an orlistat group, a PU low-dose group, a PU medium-dose group, and a PU high-dose group. The normal group was kept on routine diet and other groups continued to feed the high-fat diet. The body weight and food intake were measured and recorded weekly. After 8 weeks, the levels of the four lipids in the serum of each group of mice were determined by an automatic biochemical instrument. Oral glucose tole-rance and intraperitoneal insulin sensitivity were tested. Hemoxylin-eosin(HE) staining was applied to observe the hepatic and adipose tissues. The mRNA expression levels of peroxisome proliferators-activated receptor γ(PPARγ) and C/EBPα were determined by real-time quantitative polymerase chain reaction(Q-PCR), and the mRNA and protein expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), anterior cingulate cortex(ACC), and carnitine palmitoyltransferase 1A(CPT1A) were determined by Western blot. Finally, the body mass, Lee's index, serum total glyceride(TG), serum total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C) levels were significantly higher and high-density lipoprotein cholesterol(HDL-C) levels were significantly lower in the model group as compared with the normal group. The fat deposition in the liver was significantly increased. The mRNA expression levels of hepatic PPARγ and C/EBPα and the protein expression level of ACC were increased, while the mRNA and protein expression levels of CPT-1α(CPT1A) and AMPK were decreased. After PU treatment, the above indexes of obese mice were reversed. In conclusion, PU can decrease the body weight of obese mice and control their food intake. It also plays a role in the regulation of lipid metabolism and glycometabolism metabolism, which can significantly improve hepatic fat deposition. Mechanistically, PU may regulate liver lipid deposition in obese mice by down-regulating lipid synthesis and up-regulating lipolysis through activation of the AMPK/ACC pathway.
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Rats , Mice , Animals , Mice, Obese , AMP-Activated Protein Kinases/metabolism , PPAR gamma/metabolism , Mice, Inbred C57BL , Liver/metabolism , Obesity/genetics , Body Weight , Lipid Metabolism , Diet, High-Fat/adverse effects , Lipids , CholesterolABSTRACT
Obesity related glomerulopathy (ORG), as a disease with an increasing incidence of metabolic kidney injury, has become a new hot spot in today's society. A variety of factors are involved in the occurrence and development of ORG. Among them, the ectopic deposition of kidney lipids is not only a significant feature of ORG, but also a key link to promote the progress of ORG. This article reviews the related mechanisms of lipid deposition in ORG and the treatment of ORG with lipid deposition as the target.
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O BJECTIVE To investigate the regulatory effect of total fla vonoids of Matricaria recutita on lipid abnormalities in human hepatoma HepG 2 cells and its lipid-lowering mechanism. METHODS The high-content total flavonoids extract from M. recutita was isolated and purified by macroporous resin. HepG 2 cells were divided into control group （without administration ）， model group （without administration ），fenofibrate group （positive control ，3.61 μg/mL）and M. recutita total flavonoids low-dose ， medium-dose and high-dose groups （100，150 and 200 μg/mL）. Except for control group ，lipid deposition model of HepG 2 cells in other groups were established by 1 mmol/L mixture of oleic acid and palmitic acid. After 24 hours of intervention ，the levels of free fatty acids （FFA）in cell supernatant and triglyceride （TG）and FFA in cells were detected ；Oil red O staining was used to observe the deposition of lipid droplets in cells and detect the content of lipid ；DAPI staining was used to observe the protein expression of diacylglycerol acyltransferase 2（DGAT2）in cells ，and fluorescence intensity of protein expression of DGAT 2 were also detected ； protein expressions of key enzymes of TG synthesis as acetyl CoA carboxylase （ACC），fatty acid synthase （FAS）and DGAT 2 were detected by Western blot. RESULTS After separation and purification ，the content of total flavonoids from M. recutita increased from 6.72％ to 56.20％. The results of cell experiment showed that compared with control group ，the levels of TG and FFA in cells and FFA in the cell supernatant increased significantly in the model group ，the content of lipid in cells increased significantly，the fluorescence intensity of protein expression of DGAT 2 increased significantly ，and the protein expressions of ACC，FAS and DGAT 2 increased significantly （P＜0.01）； large number of lipid dro plets were accumulated in the cells. Compared with model group ，the levels of above indexes in M. recutita total flavonoids low-dose ， medium-dose andhigh-dose groups were significantly reversed （P＜0.01）；the accumulation of lipid droplets in cells decreased significantly. CONCLUSIONS M. recutita total flavonoids can inhibit the TG synthesis of lipid depos ition model HepG 2 cell，reduce the lipid accumulation of cells and prevent the lipid damage of cells. Its mechanism may be related to the down-regulation of the expression of ACC/FAS/DGAT 2 pathway.
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Objective:To evaluate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on lipid homeostasis and cellular injury of podocytes, and to clarify its mechanism.Methods:Twelve-week old C57BL/6 wild-type mice ( n=10) and PCSK9 knockout ( PCSK9 KO) mice ( n=10) were selected as the animal models. The renal tissues were taken after perfusion through heart. Mouse podocytes were transfected with PCSK9 siRNA to downregulate PCSK9 expression. BODIPY 493/503 staining was performed for evaluating lipid accumulation, and standard transmission electron microscopy (TEM) was used to observe the foot process of podocytes, the shape of mitochondria and lipid droplet in podocytes. TUNEL staining was carried out to evaluate cell apoptosis in glomerulus. The parameters about mitochondria function (key enzymes such as PGC-1α, CPT-1 and Acox-1) and apoptosis were quantified through qPCR and western blotting. Results:The lipid accumulation in glomerulus of PCSK9 KO mice were more serious than controls. The expression of PGC-1α protein and PGC-1α, CPT-1 and Acox-1 mRNA in PCSK9 KO mouse kidney tissues were decreased than controls (all P<0.05), and mitochondria swelling and cristae disappearance in podocytes of PCSK9 KO mice were observed. In PCSK9 KO group, the foot process of podocytes partially fused and disappeared, and the apoptosis index increased compared with the control group ( P<0.05). In vitro, compared with the control group, the lipid accumulation was more significant, transcription level of key enzymes related to mitochondrial function was decreased, mitochondrial structure was damaged and the apoptosis index was increased in cultured podocyte PCSK9 siRNA group (all P<0.05). Conclusions:PCSK9 is involved in the lipid homeostasis of podocytes. The decrease of PCSK9 results in the increase of intracellular lipid accumulation, accompanied by the mitochondrial structure damage and disfunction of podocytes, and leads to cell apoptosis.
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Objective:To investigate the effects of liraglutide on the expressions of autophagy markers LC3B, LC3B mRNA and lipid deposition in myocardial tissue of rats with early diabetes mellitus.Methods:A total of 36 healthy male Wistar rats aged 4-5 weeks and weighing (l80-200) g were selected and divided into normal group (group NC, 10 rats) and model group (26 rats) according to random number table. Rats in the NC group were fed with routine diet and rats in the model group were given high glucose and high fat diet for 12 weeks. Rats in the model group were injected with streptozotocin into the abdominal cavity in a single dose of 25 mg/kg after molding. Rats in the model group were further divided into three groups: T2DM group (group DM/NS, 9 rats, given equal volume of saline) , liraglutide intervention group (group DM/LIR, 8 rats, injected with 100 μg/kg liraglutide twice daily) and Liraglutide and Chloroquine intervention group (group DM/LIR+CQ, 8 rats, injected with 100 μg/kg liraglutide twice daily, and injected with Chloroquine 50 mg/kg once every two days) . Rats in group NC were given equal volume of saline. At the end of 12 weeks, all the rats were tested blood glucose and anaesthetized to collect myocardial tissues to observe myocardial lipid deposition and fiber arrangement under light microscope after HE staining. The expressions of LC3B were detected by immunohistochemical method, and the expressions of LC3B mRNA were detected by real-time fluorescence quantitative polymerase chain reaction method. Differences among groups were compared by one-way analysis of variance, pairwise comparison was conducted by using LSD-t test, correlation was analyzed by Pearson correlation.Results:(1) Compared with group NC, the myocardial fibers arranged in disorder, and the ratio of myocardial foam cells/total cardiomyocytes were increased, the level of LC3B mRNA and LC3B were decreased in group DM/NS and DM/LIR+CQ (in group DM/NS: 2.18±0.90 vs 11.79±0.74, 2.03±0.10 vs 1.85±0.06, 194.18±10.19 vs 175.99±6.09, t=25.24, 4.69, 3.22, respectively; in group DM/LIR+CQ: 2.18±0.90 vs 11.24±1.29, 2.03±0.10 vs 1.89±0.08, 194.18±10.19 vs 176.73±7.82, t=17.56, 4.65, 3.99, respectively, all P<0.05) . There is no difference in above indicators (2.18±0.90 vs 1.29±0.60, 2.03±0.10 vs 2.01±0.20, 194.18±10.19 vs 201.27±11.35, t=2.20, 0.28, 1.40, respectively, all P>0.05) . (2) Compared with group DM/NS, the ratio of myocardial foam cells/total cardiomyocytes, the level of LC3B mRNA and LC3B were no difference in group DM/LIR+CQ ( t=1.09, 1.18,0.22, respectively, all P>0.05) . The ratio of myocardial foam cells/total cardiomyocytes was decreased, the level of LC3B mRNA and LC3B were increased in group DM/LIR (11.79±0.74 vs 1.29±0.60, 1.85±0.06 vs 2.01±0.20, 175.99±6.09 vs 201.27±11.35, t=31.86, 2.39, 5.82, respectively, all P<0.05) . (3) The significant negative correlation were observed between the ratio of myocardial foam cells/total cardiomyocytes and LC3B mRNA, LC3B levels (r=-0.977, -0.986, respectively, all P<0.05) . Conclusion:Liraglutide can protect the myocardial structure in early diabetic rats by increasing myocardial autophagy, reducing the number of myocardial foam cells, and improving the myocardial lipid deposition.
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Aim To investigate the effect of vaccarin on mouse atherosclerosis in vivo and the underlying mechanism. Methods AopE mice aged 6 to 8 weeks old were used to establish the atherosclerosis model. Oil red O staining was used to determine the lipid levels in aorta and aortic root. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum inflammatory factors. Results Vaccarin could effectively reduce the levels of blood glucose and blood pressure in AopE
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Aim To investigate the effect of dihydromyricetin (DHM) on lipid accumulation in liver of obese mice induced by high fat diet and its mechanism. Methods Sixty C57BL/6J mices were randomly divided into six groups (n = 10); (1)ND group; normal diet, (2)ND + L-DHM group; normal diet and treatment with low-dose DHM (125 mg • kg
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Non-alcoholic fatty liver disease is a type of metabolic liver injury which is closely related to insulin resistance. Now it has become the leading cause of chronic liver diseases worldwide, which is closely related to the high incidence of type 2 diabetes and arteriosclerotic cardiovascular disease. It can progress into cirrhosis and hepatocellular carcinoma. The pathogenesis of non-alcoholic fatty liver disease is complicated and not yet fully elucidated. In recent years, studies have found that autophagy plays an important role in the development of non-alcoholic fatty liver disease, mainly through regulation of insulin resistance, endoplasmic reticulum stress, mitochondrial dysregulation, lipid-toxicity caused by lipid deposition and inflammation.
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Non-alcoholic fatty liver disease is a type of metabolic liver injury which is closely related to insulin resistance. Now it has become the leading cause of chronic liver diseases worldwide, which is closely related to the high incidence of type 2 diabetes and arteriosclerotic cardiovascular disease. It can progress into cirrhosis and hepatocellular carcinoma. The pathogenesis of non-alcoholic fatty liver disease is complicated and not yet fully elucidated. In recent years, studies have found that autophagy plays an important role in the development of non-alcoholic fatty liver disease, mainly through regulation of insulin resistance, endoplasmic reticulum stress, mitochondrial dysregulation, lipid-toxicity caused by lipid deposition and inflammation.
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Objective To observe the effect of treadmill running on skeletal muscle lipid deposition,and the expression of vascular endothelial growth factor-B(VEGFB)and its receptor in soleus muscles of high-fat diet mice.Methods Thirty-two 5-week-old C57BL/6 male mice were randomly divided into a control group(n=8)and a high-fat diet group(n=24),and fed with normal and high-fat diet respectively.Eight weeks later,16 obesity mice were selected from the latter group and randomly divided into a sedentary group(n=8)and a treadmill running group(n=8).The running group underwent treadmill running at 25 m/min for an hour every day,five days a week for 8 weeks,while the other two groups did not do any exercises.The weight was measured before the mice were killed.The soleus lipid deposition level was determined using oil red O staining,The expression of VEGFR1 and Neuropilin-1(NRP1)was determined using the immunohistochemical staining,while the mRNA expression of VEGFB,VEG-FR1,NRP1 and peroxisome proliferator-activated receptor-γcoactivator-1α (PGC-1α) was detected using the real-time PCR.Results Compared with the control group,a significant increase was observed in the weight and the soleus lipid deposition of the high-fat diet group,while there were no significant differences in the expression of VEGFB,NRP1,VEGFR1 and PGC-1α.mRNA between the two groups.Compared with the sedentary obese mice,significant decrease in the body weight and soleus lipid deposition,significant increase in VEGFR1 mRNA expression,but no significant changes in the expression of VEGFB,NRP1 and PGC-1α mRNA were observed in the treadmill-running obese mice.Conclusion The treadmill running has no effect on the VEGFR1 expression in soleus of obese mice,but significantly up-regulates the expression of its receptors.It indicates that the treadmill running can lower the intramyocellular lipid deposition as it can strengthen the VEGFB/VEGFR1 in soleus muscles.
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Objective: To study the therapeutical effect of Jiuwei Gantai Capsule (JWGT) on nonalcoholic fatty liver disease (NAFLD) of rats induced by high fat diet and its possible therapeutic mechanism. Methods: The experimental rats were divided into six groups: normal group, model group, silymarin group (0.05 g/kg), JWGT high-, mid- and low-dose groups (1.80, 0.90, and 0.45 g/kg). Except the normal group, NAFLD rats were fed with high fat diet for 10 weeks, those other groups were ig given relevant medicine from the week 5. All the rats were put to death after 10 weeks, the changes of body weight, liver weight, liver index, and hepatic histopathological morphology were observed. The high density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in serum were collected for the contents detection. Total choesterol (TC), triacylglycerol (TG), superoxide dismutase (SOD), and malondialdehyde (MDA) in hepatic tissue were detected, too. Results: Compared with the model group, the content of FFA, AST, and ALT in serum of NAFLD rats were decreased (P < 0.05), while HDL-C was obviously improved (P < 0.05) in JWGT high- and mid-dose groups. The TC, TG, and MDA in the hepatic tissue were obviously decreased (P < 0.05), while the activity of SOD was significantly improved (P < 0.05). Meanwhile, the pathological images of hepatic tissue and classified graded method of steatosis were improved in NAFLD rats. Conclusion: JWGT has the regulation of lipid and protection of liver for NAFLD rats. Its therapeutic mechanism is partly related to regulating lipid metabolism and anti-oxidative damage.
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Objective To study the effect of metformin on glucolipid metabolic disorders and liver lipid deposition caused by clozapine in rats.Methods From 1 d to 4 d,Clozapine 5 mg·kg -1 ·d -1 was gavaged,and the dose increased to 25 mg·kg -1 ·d -1 from the 5th day.Metformin 100 mg·kg -1 ·d -1 or 400 mg·kg -1 ·d -1 or simvastatin 1 mg· kg -1 ·d -1 was gavaged from the 15th day.The total period of dosing was 8 weeks.Body mass,fasting blood sugar (FBS) and postprandial 2 hours blood glucose (2hPBG)were measured at baseline,3 d,1 week,2 weeks,4 weeks,6 weeks and 8 weeks.At the end of the 8th week,serum cholesterol (TC),triglyceride (TG),low density lipoprotein (LDL -C), high density lipoprotein (HDL -C),fructosamine (FA)and insulin (IRS)were measured and liver HE staining was done.Results There were no significant differences of the measured indexes between control group and metformin group at the all test points.By the end of the 6th and 8th week,compared with control group,the body mass,FBS,2hPBG,IRS, FA,TC,TG and LDL -C were significantly increased in clozapine group (P <0.05 ),while HDL -C decreased in clozapine group (P <0.05).Compared with clozapine group,body mass,FBS,2hPBG,IRS,FA,TC,TG and LDL -C were significantly decreased by metformin or simvastatin administration (P <0.05),while HDL -C increased(P <0.05).Rat liver cells in clozapine group were not neat around the small blood vessels;there were more white fat cells and hepatocellular lipid calm far away from the blood vessels.However,in other groups,there were moderate white fat cells, and there were not much hepatocellular lipid calm far away from the blood vessels.Conclusion Metformin could effectively prevent and treat weight gain,glucolipid metabolic disorder and liver lipid deposition caused by clozapine.
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Aims: To determine the anti-hyperglycaemic and anti-hyperlipidaemic effects of glycyrrhizic acid (GA), the root extract of Glycyrrhiza glabra in rats with switching type of diet i.e. between normal diet (ND) and high-fat diet (HFD). Study Design: In vivo study. Place and Duration of Study: School of Science, Monash University Sunway Campus between January 2010 and October 2010. Methodology: Sixteen Sparague-Dawley rats were divided into two groups having eight animals each i.e. group A- ND+GA→ HFD+GA; group B- ND+GA→HFD+no GA. Rats were fed with the corresponding diet and GA (100 mg/kg) for 28 days. The blood glucose, insulin and triacylglycerol levels, lipoprotein lipase expression in the liver, kidney, heart, abdominal muscle (AM), quadriceps femoris (QF), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) and tissue lipid deposition were measured. Results: No significant difference in blood glucose levels between groups. GA significantly lowered (P=.05) triacylglycerol in rats fed on a ND with GA and later switched to a HFD without GA (group B) compared to rats fed on a ND with GA and later switched to a HFD with continuous GA supplementation (group A). For LPL expression, group B had significant lower (P=.05) LPL expression in the liver, AM, kidney and heart than group A. Group A had significantly smaller (P=.05) size of VAT than group B. Conclusion: These findings may indicate the role of GA in lowering blood glucose and triacylglycerol in subjects who had a switch from a ND with GA to a HFD without GA but not in those who had a switch from a ND with GA to a HFD with continuous GA supplementation.
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AIM:To investigate the effect of insulin and gliclazide therapies on the liver fat accumulation in type 2 diabetic rats .METHODS:A high-fat diet plus low-dose streptozotocin was implemented to establish a type 2 dia-betic rat model, and the rats were randomly divided into diabetes mellitus (DM) group, diabetic rats treated with insulin ( INS) group, diabetic rats treated with gliclazide per os ( PO) group, and normal control ( NC) group.The diabetic rats in INS group and PO group were given insulin and gliclazide for 3 weeks, respectively.The changes of the liver fatty were evaluated with oil red O staining .Fasting plasma adiponectin concentration was measured by ELISA .The expression of adi-ponectin receptor 1 ( AdipoR1 ) was detected by real-time PCR.The protein levels of AMP-activated protein kinase (AMPK), phosphorylated AMPK on threonine 172 ( Thr172p-AMPK), sterol regulatory element-binding protein 1c (SREBP-1c), phosphorylated SREBP-1c on serine 372 (Ser372p-SREBP-1c), acetyl-CoA carboxylase (ACC), phospho-rylated ACC on serine79 (Ser79p-ACC) and immunoglobulin-binding protein (BiP) in the liver homogenate were deter-mined by Western blotting .RESULTS:Compared with the normal rats , in DM group, the presence of cytoplasmic lipid deposits was confirmed by oil red O staining .In INS group, these changes were significantly lower than those in DM group . Similar results were obtained in PO group .Insulin therapy significantly increased the plasma concentration of diponectin and liver tissue levels of AdipoR1 compared with DM group.At the same time, these 2 indicators returned to normal levels after gliclazide therapy .Thr172p-AMPK/AMPK, Ser372p-SREBP-1c/SREBP-1c and Ser79p-ACC/ACC expression ratios were significantly reduced in DM group compared with control values .The expression of BiP was increased on the contrary . After insulin therapy, Thr172p-AMPK/AMPK and Ser372p-SREBP-1c/SREBP-1c were significantly increased, and Ser79p-ACC/ACC and BiP returned to the normal levels .After gliclazide treatment, Thr172p-AMPK/AMPK and Ser372p-SREBP-1c/SREBP-1c returned to the normal levels , the expression ratio of Ser79p-ACC/ACC had no significant improve-ment compared with DM group , and the expression of BiP significantly declined .CONCLUSION: Both the insulin and gliclazide therapies reduce the lipid deposition in the liver of rats with type 2 diabetes by activating AMPK , but the extent and mechanism are not the same.In insulin therapy, AMPK restrains the expression of SREBP-1c directly, increases the phosphorylation of SREBP-1c, and affects SREBP-1c by inhibiting the endoplasmic reticulum stress .Gliclazide treatment, which has no effect on the lipid oxidation , reduces lipid deposition in the liver only through the phosphorylation of SREBP-1c and the suppression of the endoplasmic reticulum stress .