[Show abstract][Hide abstract] ABSTRACT: To investigate the semi-quantitative method for evaluating lipid accumulation in livers, male C57BL/6J mice (CON), HFD mice characterized with the mild fatty liver induced by high-fat diet, and KKAy mice charactered with the moderately severe fatty liver induced by high-caloric diet were used. The lipid accumulation was estimated by the histological examination (HE staining) and the content of hepatic triglyceride, separately. Echo-intensity of two selected regions along the ultrasound transmission direction was recorded using a small animal ultrasonographic system, and the echo-intensity attenuation coefficient was calculated. Correlation between the echo-intensity attenuation coefficient and the content of hepatic triglyceride was analyzed by the Spearman's rank correlation analysis. The results showed that the lipid accumulation in livers increased significantly in both HFD and KKAy mice compared with CON mice and it was more serious in KKAy mice than that in HFD mice. The values of echo-intensity attenuation coefficient were also increased in sequence according to group. These values were positively associated with the content of hepatic triglyceride (r = 0.744, P < 0.01). In conclusion, the echo-intensity attenuation coefficient is a simple, impersonal, and non-invasive method for evaluating the hepatic lipid accumulation. It can be used to research the process and the treatment of fatty liver diseases in mice.
No preview · Article · Oct 2014 · Yao xue xue bao = Acta pharmaceutica Sinica
[Show abstract][Hide abstract] ABSTRACT: To explore the effects of serum insulin on the expression of ChREBP, ACC and FAS in vivo, KKAy mice which were characterized with high levels of both serum insulin and glucose and DIO mice which were characterized with high serum insulin level alone were utilized, separately. The age-matched C57BL/6J mice fed with standard chow were used as normal control (Con). Expressions of hepatic ChREBP, ACC and FAS were detected by Western blotting. As the results, in KKAy mice, a positive correlation between the levels of serum insulin and glucose (r = 0.902, P < 0.000), as well as between the levels of serum insulin and TG (r = 0.732, P < 0.000), was observed. Meanwhile, the expressions of hepatic ChREBP, ACC and FAS increased significantly and accompanied with its hyperinsulinemia and hyperglycemia, separately. In DIO mice, correlation between the levels of serum insulin and TG (r = 0.722, P < 0.001) also showed positive, and the expressions of hepatic ChREBP, ACC and FAS increased significantly and also accompanied with its hyperinsulinemia. However, their blood glucose values were almost normal. These demonstrated that hyperinsulinemia may cause glycolipid metabolic disorders by up-regulating the expression of ChREBP in vivo.
No preview · Article · Jun 2014 · Yao xue xue bao = Acta pharmaceutica Sinica
[Show abstract][Hide abstract] ABSTRACT: This study is to investigate the effects of a Chinese prescription (FF), compatibility of Rhodiola crenulata, Cordyceps militaris and Rheum palmatum, on nephropathy in type 1 diabetic rats induced by streptozocin. According to fasting blood glucose level, diabetic rats were divided into three groups: model group, insulin-treated group and FF-treated group. Parameters for evaluating the glucose & lipid metabolism and the renal function were monitored dynamically. Levels of oxidative stress were detected ten weeks later. The results show that FF could significantly decrease the level of serum glucose and lipid profiles, improve the renal functions by decreasing blood urea nitrogen, urine albumin excretion and urease activity; FF could also affect on oxidative stress. In conclusion, Chinese prescription FF could ameliorate hyperglycemia-mediated renal damage in type 1 diabetic rats. These effects may be related to its regulation on the metabolism of glucose and lipid, the microcirculation disturbance and the oxidative stress.
No preview · Article · Nov 2013 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
[Show abstract][Hide abstract] ABSTRACT: To investigate the mechanisms of a compound (FF16), compatibility of Rhodiola crenulata, Cordyceps militaris, and Rheum palmatum, on glucose metabolic disorders, the IRF mice charactered with insulin resistance and glucose metabolic disorders induced by high-fat diet in C57BL/6J mice were randomly divided into 3 groups; IRF, rosiglitazone (Rosi) and FF16. The glucose metabolism was evaluated by fasting blood glucose (FBG) levels and intraperitoneal glucose tolerance test (IPGTT). The insulin sensitivity was estimated by insulin tolerance test (ITT), fasting serum insulin levels and the index of HOMA-IR. The expressions of Akt and its phosphorylation levels, GSK3beta and its phosphorylation levels in liver were detected by Western Blot. The results showed that FF16 significantly improved the glucose metabolic disorders through reducing FBG by 15.1%, decreasing AUC values in glucose tolerance tests by 22.3%. FF16 significantly improved the insulin sensitivity through decreasing AUC values in insulin tolerance tests by 22.1%, reducing the levels of serum insulin by 42.9% and of HOMA-IR by 49.5%, comparing with model control, respectively. After the treatment with FF16, the levels of p-Akt and p-GSK3beta were increased by 116.4% and 24.9%, respectively, in the liver of IRF mice. In conclusion, compound FF16 could improve glucose metabolic disorders in IRF mice through enhancing the glyconeogenesis.
No preview · Article · Jun 2013 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
[Show abstract][Hide abstract] ABSTRACT: To investigate the effects of a compound (FF16), compatibility of Rhodiola crenulata, Cordyceps militaris, and Rhum palmatum, on non-alcoholic fatty liver disease in IRF mice induced by high fat diet H&E stain was processed to evaluate the lipid accumulation in liver, and the dynamic microcirculation observation system was applied to determine hepatic microcirculation of IRF mice. Western blot was performed to evaluate IRS-2, HSL and ppar-alpha expression in liver. The results demonstrate that FF16 significantly decreased the liver lipid index and improved liver steatosis in IRF mice. Furthermore, FF16 could ameliorate hepatic microcirculation disturbance in IRF mice through enhancing RBC velocity and shear rates by 62.5% and 49.7%, increasing sinusoids perfusion by 70.0%, inhibiting adhered leukocytes in IRF mice. The abnormal expressions of IRS-2 and HSL were both reversed by the administration of FF16. In conclusion, FF16 could improve non-alcoholic fatty liver disease in IRF mice by improving insulin sensitivity, regulating lipid metabolism and improving microcirculation disturbance.
No preview · Article · Jun 2013 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
[Show abstract][Hide abstract] ABSTRACT: Base on the improvement of compound FF16, compatibility of Rhodiola crenulata, Cordyceps militaris, and Rheum palmatum, on both insulin resistance and obesity, its effects on type 2 diabetes (T2DM ) was investigated here. The results showed that the levels of fasting and no-fasting blood glucose were controlled in the spontaneous type 2 diabetes KKAy mice; the impaired glucose tolerance (IGT)was improved by decreasing significantly the values of the glucose peaks and the area under the blood glucose-time curve (AUC ) after glucose-loading in glucose tolerance test (OGTT) in both high-fat-diet-induced pre-diabetes IRF mice and KKAy mice, respectively. The pancreatic histopathological analysis showed that the increased islet amount, the enlarged islet area, and the lipid accumulation in the pancreas were reversed by FF16 treatment in both IRF mice and KKAy mice. In the palmitate-induced RINm5f cell model, FF16 could effectively reduce the apoptosis and enhance the glucose-stimulated insulin secretion, respectively. In conclusion, FF16 could improve the T2DM by protecting the pancreatic beta-cells.
No preview · Article · May 2013 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
[Show abstract][Hide abstract] ABSTRACT: Rhein (RH), a compound purified from Radix et Rhizoma Rhei, has been used to alleviate liver and kidney damage. It is found that RH inhibited the differentiation of 3T3-L1 preadipocytes induced by differentiation medium in a time- and dose-dependent manner. It was revealed that RH downregulated the expression of adipogenesis-specific transcription factors PPARγ and C/EBPα, as well as their upstream regulator, C/EBPβ. Furthermore, the PPARγ target genes that are involved in adipocyte differentiation, such as CD36, aP2, acyl CoA oxidase, uncoupled protein 2, acetyl-CoA carboxylase, and fatty acid synthase, were reduced after to RH. In addition, high-fat diet-induced weight gain and adiposity were reversed by RH in C57BL/6 mice. Consistent with the cells' results, RH downregulated the mRNA levels of PPARγ and C/EBPα, and their downstream target genes in C57BL/6 mice. Taken together, adipocyte differentiation and adipogenesis were inhibited by RH in cultured cells and in rodent models of obesity. The evidence implied that RH was a potential candidate for preventing metabolic disorders.
Full-text · Article · Aug 2011 · Journal of Asian natural products research
[Show abstract][Hide abstract] ABSTRACT: To investigate the semi-quantitative method for evaluating the lipid accumulation in pancreas, the KKAy mice, a classical type 2 diabetes mellitus model mice, were used and treated with rosiglitazone (Rosi); and the age-matched C57BL/6J mice were used as normal control. Pancreas was fixed quickly for histological examination with HE staining. For the estimation of the lipid accumulation in pancreas, semi-quantitative method was designed: the number and the size of islet, lipid accumulation in islet and in exocrine gland were observed and the integrative score calculated under the microscope, separately. In KKAy mice, the characteristics of the increased amount of islet, the enlarged area of islet, an abundance of large vacuolations, lipid droplets, and fat proliferation were exposed frequently, and the integrative score increased 2.1 folds compared with that in C57BL/6J mice. Meanwhile, the levels of serum glucose, insulin, and triglyceride (TG) were 1.7, 18.0, and 9.0 times as those in C57BL/6J mice, respectively. With the rosiglitazone (10 mg x kg(-1)) treatment, compared with that in KKAy mice, the pancreatic pathological changes were ameliorated significantly, and the integrative score in KKAy + Rosi mice decreased by 28.9%; and the levels of serum glucose, insulin, and triglyceride decreased by 48.3%, 81.3% and 64.1%, respectively. It showed there is a correlation between the pancreatic pathological semi-quantitative score and the values of serum parameters. In conclusion, this semi-quantitative scoring method is simple and objective for the evaluation of lipid accumulation in pancreas of mice.
No preview · Article · Jun 2011 · Yao xue xue bao = Acta pharmaceutica Sinica
[Show abstract][Hide abstract] ABSTRACT: PTP1B is a negative regulator of insulin signaling pathway. This study investigated the effects of compound CCF06240, a PTP1B inhibitor, on insulin sensitivity and lipid metabolic abnormalities in vivo and in vitro, respectively. The insulin resistant IRM mouse model was induced by HFD. The responses to insulin were determined by OGTT, ITT, and hyperinsulinemic-euglycemic clamp test. The body weight and the levels of serum TC and TG were measured to estimate the lipid metabolism in vivo. Recombinant human GST-PTP1B protein was used to measure the inhibition of CCF06240 on PTP1B activity. The hepatocyte lipid accumulation was induced by high concentrations of FFA and insulin in HepG(2) cells, and evaluated by the Oil Red O method. In IRM mice, the insulin resistance was improved; the body weight and the levels of TC and TG were also reduced by oral CCF06240 administration. In lipid accumulated model cells, CCF06240 was found to reverse the increased PTP1B activity, enhance the insulin-induced tyrosine phosphorylation in insulin signaling pathway, attenuate the FFA-insulin-induced cellular lipid accumulation, and down-regulate the expressions of genes related fatty acid synthesis. These results demonstrated that the PTP1B inhibitor, compound CCF06240, could increase insulin sensitivity through the regulation of insulin signaling pathway, and decrease FFA-insulin-induced hepatocytes lipid accumulation by reducing fatty acid syntheses.
No preview · Article · May 2011 · Molecular and Cellular Biochemistry