Decreased body-fat accumulation and increased vasorelaxation to glyceryl trinitrate in middle-aged male rats following six-weeks consumption of coconut milk protein

Abstract We investigated whether coconut milk protein (CMP) contributes to the beneficial effects of coconut milk consumption on cardiovascular health markers previously found in middle-aged rats. CMP was isolated and precipitated from dried fresh coconut milk, then gavaged (1 g/kg) to middle-aged male rats for six weeks; control rats received distilled water. Compared to controls, CMP caused decreased body fat and lipid accumulation in liver cells and the platelet count. CMP did not affect basal blood pressure or heart rate in anesthetized rats. Vascular responsiveness to phenylephrine, DL-propargylglycine (PAG), acetylcholine or sodium nitroprusside was unaffected, but vasorelaxation to glyceryl trinitrate (GTN) increased. Effects of ODQ on vasorelaxation to GTN were similar in both groups. Expression of blood vessel eNOS, CSE and sGC was normal. The cyclic guanosine monophosphate (cGMP) level of CMP-treated rats was normal but addition of GTN increased cGMP and NO concentration more in CMP-treated rats than in controls, an effect unaltered by addition of diadzin. Taken together, CMP appears partially responsible for the improvement in cardiovascular health markers caused by coconut milk in middle-aged male rats

Total Flavonoids of Mulberry Leaves Improves Liver Lipid Metabolism in Type 2 Diabetic Rats by Regulating PPAR-α/CPT-1 Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 （T2DM） rats， and the mechanism based on liver peroxidase proliferators activate receptors-α （PPAR-α） and carnitine palmityl transferase-1 （CPT-1） proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet （HFD） + streptozocin（STZ）method. Rats with blood glucose ≥ 11.1 mmol·L-1 were divided into three administration groups with the high dose （300 mg·kg-1）， medium dose （150 mg·kg-1）， and low dose （75 mg·kg-1） of total flavonoids of mulberry leaves for 8 weeks， respectively， to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin （HE） staining. Biochemical method was used to detect the levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein-cholesterol （LDL-C）， and high density lipoprotein-cholesterol （HDL-C） of blood lipid metabolism in rats. The messenger ribonucleic acid （mRNA） and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves， compared with the control group， the food intake， liver index， and fasting blood glucose of rats in the model group increased significantly （P<0.01）. Compared with the model group， the food intake， fasting blood glucose， and liver index of rats in the administration groups decreased significantly （P<0.01）. The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group， the levels of TC， TG， and LDL-C increased significantly （P<0.01）， but the level of HDL-C decreased significantly （P<0.01） in the model group. Compared with the model group， the levels of TC， TG， and LDL-C decreased significantly （P<0.05， P<0.01）， whereas the level of HDL-C increased significantly （P<0.01） in the administration groups. The results of Real-time PCR showed that compared with the control group， the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.01）. The results of Western blot showed that compared with the control group， the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.05， P<0.01）. ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.

Effects of different exercise on liver lipid accumulation and FGF21 secretion in obese rats / 中国应用生理学杂志

Objective: To investigate the effects of continuous exercise training (CT) and high-intensity interval exercise training (HIIT) on liver lipid metabolism and the correlation of the level of fibroblast growth factor 21(FGF21) in serum and liver tissues. Methods: Male SD rats were randomly divided into normal diet group (N) and obesity model group (H) after 1 week of adaptive feeding. Rats in the obesity model group were fed with 45% high-fat diet for about 8 weeks, and 20% weight increase compared with normal rats was considered as obesity. The rats were divided into normal diet control group (LC), normal diet HIIT group (LHI), normal diet CT group (LCT), High fat diet-induced obese control group (OC), obese HIIT group (OHI), and obese CT group (OCT) (n=10). Exercised rats were given weight-bearing swimming training intervention for 8 weeks. Blood samples were collected at least 24h after the last exercise intervention to detect the serum levels of inflammatory factors and FGF21. Liver tissue samples were collected to detect the lipid content, lipid metabolic enzyme content and FGF21 expression level. Results: Compared with LC group, the body weight, serum inflammatory factors levels and hepatic triglyceride content were increased significantly (P＜0.05). Hepatic triglyceride content was downregulated in LHI group and FGF21 expression level was enhanced in LCT group (P＜0.05). Compared with OC group, the body weight and hepatic triglyceride content were decreased significantly (P＜0.05), mitochondrial CPT-1β and β-HAD enzyme contents in liver were increased significantly (P＜0.05) in OHI group, the contents of LPL and FAT/CD36 enzyme in liver and the levels of FGF21 in serum and liver of OCT group were increased significantly (P＜0.05). Conclusion: Both exercise modes can reduce the body weight in normal and obese rats, and lipid deposition in the liver of obese rats. HIIT has a more significant effect on alleviating liver lipid deposition in obese rats by upregulating mitochondrial lipid oxidation level in normal and obese rats. CT improves the levels of FGF21 in serum and liver tissues of normal and obese rats, enhances enzyme contents that involved in fatty acids uptake to the liver, which has limited effect on alleviating lipid deposition in liver of obese rats.

Effect and mechanism of muscle injury on liver lipid metabolism in Duchenne muscular dystrophy mice / 中国药科大学学报

@#Duchene muscular dystrophy (DMD) is a serious progressive muscular dystrophy.Reports in recent years about abnormal lipid in DMD patients have increased, yet little attention has been paid to liver lipid.This study aimed to explore the effect of dystrophin gene defect on liver lipid synthesis.7-week-old mdx male mice were used as DMD model.The conditions of liver function, liver lipid accumulation and liver lipid synthesis were determined through liver tissue morphological examination, blood biochemical examination, and detection of hepatic gene and protein expression.The results showed that lipid droplets in liver of mdx mice increased significantly.The contents of total cholesterol and triglyceride in liver, aspartate aminotransferase and alanine aminotransferase in serum increased.The gene and protein expression of hepatic lipid synthesis-related enzymes such as fatty acid synthase, acetyl CoA carboxylase, and sterol regulatory element binding protein 1-c were up-regulated.These results showed accumulation of liver lipid in 7-week-old mdx male mice.

The effects of photoperiodism and exposure to bisphenol A on hepatic lipid metabolism in female mice / 中国职业医学

OBJECTIVE: To analyze the effects and the underlying mechanisms of photoperiodism and exposure to bisphenol A(BPA) on hepatic lipid metabolism in female mice. METHODS: A 2×2 factorial design was used. The photoperiod factor was set to fixed and shifted photoperiod, and the BPA factor was set to BPA exposure(BPA group) and non-exposure(control group). Specific pathogen free female C57 BL/6 J mice were randomly divided into four groups: fixed photoperiod control group, shifted photoperiod control group, fixed photoperiod BPA group, and shifted photoperiod BPA group, with eight rats in each group. The fixed photoperiod mice received a 12 ∶12 hours light-dark cycle, and the shifted photoperiod mice experienced reversed light-dark cycle once a week. Mice in BPA group were administered a dose of BPA 50 μg/kg body weigh by gavage, while mice in control group were given a equal volume of corn oil, once per day, five days per week for 12 weeks. The body weight of mice was measured during the experiment. After 12 weeks, all mice in each group were sacrificed. Plasma was collected and the levels of biochemical parameters were measured. Liver tissues were separated for examination of lipid deposition using oil red O and hematoxylin-eosin staining, and plasma triglyceride levels were measured. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA relative expression of genes of fat metabolism in liver tissues. RESULTS: At the end of the experiment, the body weights of mice were higher than that before the experiment(all P<0.05), but there was no statistically significant difference in body weights among the four groups(all P>0.05). The levels of plasma glucose, triglyceride and activity of alanine aminotransferase were higher in shifted photoperiod mice than that in the fixed photoperiod mice(all P<0.05). The plasma aspartate transaminase level was higher in BAP group than that in control group(P<0.01). The area of lipid staining in hepatic tissue was larger in the shifted photoperiod control group, fixed photoperiod BPA group and shifted photoperiod BPA group(all P<0.05), and hepatic lipid droplets aggregation was increased in these three groups compared with the fixed photoperiod control group. The mRNA relative expression of acetyl-coenzyme A carboxylase alpha(Acaca) was higher in the fixed photoperiod BPA and shifted photoperiod control groups(all P<0.05), compared with the fixed photoperiod control group. The relative expression of Acaca mRNA was lower in the shifted photoperiod BPA group than that in the fixed photoperiod BPA group(P<0.05). The mRNA relative expression of sterol regulatory element binding protein(Srebp) 1 and Srebp2 were significantly higher in the BPA group than that in the control group(all P<0.05). CONCLUSION: Both the single shifted photoperiod or BPA exposure can increase hepatic lipid deposition in female mice. The mechanism may be related to up-regulation of the mRNA expression of Acaca, Srebp1 and Srebp2. The shifted photoperiod in combination of BPA exposure has an antagonistic effect on the expression of Acaca mRNA in liver tissues of female mice.

Effects of total flavonoids in Astragali Complanati Semen on liver lipid level and ERα expression on liver in hyperlipidemia rats with kidney-Yang deficiency pattern / 中国中药杂志

Menopausal women appear lipid metabolism disorder with the ovarian function decline and the estrogen levels decreased. Modern clinical usually use estrogen replacement therapy and with long time application with lots of side effect appear. Traditional Chinese medicine has more secure and effective methords,using warming Yang drugs and methods. And the previous study proves the Chinese medicine Astragali Complanati Semen water extraction has a good role in regulation of blood lipids. Because of the liver is the most important organ on regulating metabolism, therefore this study aimed to evaluate the effects of total flavonoids in Astragali Complanati Semen(TFS)on liverlipid level and ERα expressionon liver in hyperlipidemia rats with kidney-Yang deficiency pattern to explore the substance basis and mechanism of Astragali Complanati Semen in regulate lipid effect and clarify traditional Chinese medicine advantages and features. This experiment uses hyperlipidemia rats with kidney-Yang deficiency pattern with bilateral ovariectomized and fed with high fat diet for 6 weeks. And rats of sham operation group and model group rats were intragastrilly(ig) with saline, estrogen group were intragastrilly with estrogen(0.2 mg·kg⁻¹). And three TFS group were intragastrilly with TFS at dose 28.5, 57, 114 mg·kg⁻¹ for 8 weeks. At the same time, TC, TG, LDL-C,HDL-C liver weight, liver index, uterine weight, uterine index, serum estrogen level, FSH levels and liver pathology, liver estrogen receptor expression were detected, weighting and calculating their organ index. The experimental results compared with the model group, TFS 114 mg·kg⁻¹ decreased the level of liver TG (<0.05), TC (<0.001) and LDL-C (<0.001) and increased the level of HDL-C (<0.05). Compared with the model group, estrogen group increased the level of blood serum (<0.001) and decreased the level of FSH (<0.001). In addition, compared with sham operation group,model group decreased the protein expression of ERα（<0.01）. Compared with the model group, estrogen group increased the protein expression of ERα significantly（<0.001）.TFS mid-dose group and TFS high-dose group is increased the protein expression of ERα（<0.01, <0.001）.In a conclusion,Flavonoids is the main active ingredient of Astragali Complanati Semen. The mechanism of it maybe is enhancing the estrogen receptor sensitivity or the number of estrogen receptors, amplifying the signal after the receptor conduction, which could result in lipid-lowering effect.

Endoplasmic reticulum stress and non-alcoholic fatty liver disease / 国际药学研究杂志

The“two-hit”theory which underlies the mechanism of non-alcoholic fatty liver disease (NAFLD) is difficult to explain the progress of NAFLD from liver lipid accumulation to steatohepatitis, liver fibrosis and the gradually aggravated diseases.Recently the“multiple-hit”theory emphasizes the significance of endoplasmic reticulum stress (ERS) in the progression of NAFLD. The endoplasmic reticulum is a cytoplasmic organella for protein and lipid synthesis. ERS, which can be induced by the unbalance of endoplasmic reticulum homeostasis, plays a critical role in hepatocyte lipid metabolic disorders, Apoptosis and the progression of NAFLD. In this paper, the relevance of ERS and non-alcoholic liver lipid accumulation, steatohepatitis and hepatocyte apoptosis is reviewed.

Fatty liver diseases, bile acids, and FXR

The prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide has increased at an alarming rate, which will likely result in enormous medical and economic burden. NAFLD presents as a spectrum of liver diseases ranging from simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even to hepatocellular carcinoma (HCC). A comprehensive understanding of the mechanism(s) of NAFLD-to-NASH transition remains elusive with various genetic and environmental susceptibility factors possibly involved. An understanding of the mechanism may provide novel strategies in the prevention and treatment to NASH. Abnormal regulation of bile acid homeostasis emerges as an important mechanism to liver injury. The bile acid homeostasis is critically regulated by the farnesoid X receptor (FXR) that is activated by bile acids. FXR has been known to exert tissue-specific effects in regulating bile acid synthesis and transport. Current investigations demonstrate FXR also plays a principle role in regulating lipid metabolism and suppressing inflammation in the liver. Therefore, the future determination of the molecular mechanism by which FXR protects the liver from developing NAFLD may shed light to the prevention and treatment of NAFLD.

The effects of metformin on glucolipid metabolic disorders and liver lipid deposition caused by clozapine in rats / 预防医学

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.

EFFECTS OF HIGH LEVELS OF VITAMIN E ON SERUM AND LIVER LIPIDS AND ITS PEROXIDATION IN RATS / 营养学报

The mature Wistar rats were fed with high lipid diet for 8 weeks together with 3 levels (30, 60, or 120mg/day) of dl-?-tocopheryl acetate supplementation. At the end of the experiment, serum vitamin E and lipids were measured by fluorescence analysis and enzymologic method, liver crude fat was measured by Soxhlet method, liver glycogen content and fat accumulation in parenchymal cells were estimated by histo-chemical procedure and liver lipid peroxidation was evaluated by fluorescence analysis respectively. The results showed that the high lipid diet induced hypercholesterolemia and fatty liver associated with a decrease in serum high density lipoprotein cholesterol and an increase in liver peroxidation. Overall vitamin E caused no significant decrease in serum cholesterol and triglyceride levels and no significant increase in high density lipoprotein cholesterol level, except serum vitamin E level had a positive correlation with serum cholesterol level, but could inhibit the neutral fat accumulation in liver cells and liver peroxidation in rats.The levels of serum cholesterol, or the serum vitamin E and VE/CHO were higher in females than those in males significantly when dl-a-tocopheryl acetate was given to the rats fed with high lipid diet.