Piperine regulates the circadian rhythms of hepatic clock gene expressions and gut microbiota in high-fat diet-induced obese rats

The interplay between the host circadian clock and microbiota has significant influences on host metabolism processes,and circadian desynchrony triggered by high-fat diet(HFD)is closely related to metabolic disorders.In this study,the modulatory effects of piperine(PIP)on lipid metabolism homeostasis,gut microbiota community and circadian rhythm of hepatic clock gene expressions in obese rats were investigated.The Sprague-Dawley(SD)rats were fed with normal diet(ND),HFD and HFD supplemented with PIP,respectively.After 9 weeks,rats were sacrificed with tissue and fecal samples collected for circadian analysis.Results showed that chronic PIP administration ameliorated the obesity-induced alterations in lipid metabolism and dysregulation of hepatic clock gene expressions in obese rats.The gut microbial communities studied through 16S rRNA sequencing showed that PIP ameliorated the imbalanced nicrobiota and recovered the circadian rhythm of Lactobacillaceae,Desulfovibrionaceae,Paraprevotellaceae,and Lachnospiraceae.The fecal metabolic profiles indicated that 3-dehydroshikimate,cytidine and lithocholyltaurine were altered,which were involved in the amino acid and fatty acid metabolism process.These findings could provide theoretical basis for PIP to work as functional food to alleviate the lipid metabolism disorder,circadian rhythm misalignment,and gut microbiota dysbiosis with wide applications in the food and pharmaceutic industries.

Effects of Maternal Linseed Oil Supplementation on Metabolic Parameters in Cafeteria Diet-induced Obese Rats

Because linseed oil may influence maternal and fetal metabolisms, we investigated its role in the modulation of lipid metabolism in cafeteria diet-induced obese rats and their offspring. Female Wistar rats were fed control or cafeteria food, which were either supplemented or not supplemented with linseed oil （5%） for I month before and during gestation. At parturition, serum and tissue lipids and enzyme activities were analyzed. Cafeteria diet induced adverse metabolic alterations in both mothers and offspring. Linseed oil improved metabolic status. In conclusion, linseed oil displayed health benefits by modulating tissue enzyme activities in both obese mothers and their newborns.

Efficacy of Antisense Oligodeoxynucleotide of Neuropeptide Y Y5 Receptor on Treating of Hyperleptinemia by Intraventricular Administration in Diet-induced Obese Rats

Objective: To study the efficacy of antisense oligonucleotide of neuropeptide Y (NPY) Y5 receptor on treating hyperleptinemia by intracerebral ventricular administration in diet-induced obese rats.Methods: The obese rats were prepared by feeding a high-nutritive diet for 7 weeks. The lateral ventricle of obese rats was cannulated. Either 10 μl of different neuropeptide Y Y5 receptor oligodeoxynucleotide, including antisense, sense and missense oligodeoxynucleotide (5 g/L) or 10 μl saline was administered into the ventricle through cannula three times per day in every rat. Two days later the rats were slaughtered .The weights of both retroperitoneal and epididymal adipose tissues were measured, and the serum insulin and leptin were detected by radioimmunoassay method and the murine leptin ELISA kit respectively. Results: ①The level of serum was significantly higher in experimental rats than that in normal rats. Similarly, the level of serum insulin and the weights of both retroperitoneal and epididymal adipose tissues were increased in experimental rats. ②After the diet-induced obese rats were intraventricularly administered with NPY Y5 receptor antisense oligodeoxynucleotide, the levels of serum leptin and insulin were significantly decreased and combined with the reduction of weight in retroperitoneal adipose tissue. There was, however, no significant difference in the weight of epidymal adipose tissue between pre-treated and post-treated duration. ③There was significant positive correlation among the level of serum leptin, the level of serum insulin and the weight of retroperritoneal adipose tissue in diet-induced obese rats. Conclusion: Intracerebral ventricular administration of antisense oligodeoxynucleotide of neuropeptide Y Y5 receptor may alleviate hyperleptinemia in diet-induced obese rats and decrease the weight of retroperitoneal adipose tissue and the level of serum insulin.

Monascus pilosus-fermented black soybean inhibits lipid accumulation in adipocytes and in high-fat diet-induced obese mice

Objective:To explore the anti-obesity effects and the mechanism of action of Monascus pilosus(M.pilosus)-fermented black soybean(MFBS)extracts(MFBSE)and MFBS powders(MFBSP)in adipocytes and high-fat diet(HFD)-induced obese mice,respectively.Methods:Black soybean was fermented with M.pilosus,and the main constituents in MFBS were analyzed by HPLC analysis.In vitro,MFBSE were examined for anti-adipogenic effects using Oil-Red O staining.In vivo,mice were fed a normal-fat diet(NFD)control,HFD control or HFD containing 1 g/kg MFBSP for 12 weeks,and then body weight gain and tissues weight measured.Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects.Results:MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity.MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice.MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes,such as peroxisome proliferator-activated receptorγ(PPARγ),fatty acid-binding protein 4(FABP4),and fatty acid synthase(FAS),in adipocytes and in white adipose tissue(WAT)of HFD-induced obese mice.Conclusions:These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFDinduced obese mice.

Pandanus amaryllifolius leaf extract increases insulin sensitivity in high-fat diet-induced obese mice

Objective: To examine the effect of Pandanus amaryllifolius(P. amaryllifolius) leaf extract on the insulin resistance state in obese ICR mice.Methods: Obesity was induced in mice fed with high-fat diet(45% fat) for 12 weeks. After the first six weeks on the diet, the obese mice were administered with the water extract of P. amaryllifolius leaf at 125 and 250 mg/kg/day, respectively for another six weeks. At the5 th week of treatment, oral glucose tolerance test was conducted. After six weeks of treatment, the levels of blood glucose, serum insulin, leptin, adiponectin, and lipid profiles were determined. The liver, muscle and epididymal fat tissues were removed for measuring the biochemical parameters and protein expression, as well as histological examination.Results: Six weeks of treatment with P. amaryllifolius led to a significant reduction in the blood glucose level as well as improvement in the insulin resistance. P. amaryllifolius also increased the liver glycogen storage and serum adiponectin and decreased the serum leptin levels. A reduction in the serum and hepatic triglyceride, and non-esterified fatty acid levels was also observed. The histological examination showed that the obese mice treated with P. amaryllifolius reduced the lipid droplet in liver tissue and adipocyte size in epididymal fat tissue. The treatment also increased the protein expression of glucose transporter 4 in the muscle and fat tissues.Conclusions: The treatment with P. amaryllifolius could decrease several parameters of impaired glucose and lipid metabolism. To the best of our knowledge, this is the first report on the role of P. amaryllifolius leaf extract in alleviating the insulin dysfunction in obesity state.

Anti-Obesity, Anti-Atherosclerotic and Anti-Oxidant Effects of Pu-Erh Tea on a High Fat Diet-Induced Obese Rat Model

Pu-erh tea, a traditional Chinese beverage, has been believed to have many benefits to human health and without side effects. In this study, we systematically analyzed the main active components of Pu-erh tea and investigated its anti-obesity, anti-atherosclerotic and anti-oxidant effects using an obese rat model. Obesity was induced by feeding a high-fat diet and subsequently the experimental obese mice were fed with high-fat diet supplemented with low (2.5%), medium (5%) or high (7.5%) doses of Pu-erh tea powder for 6 weeks respectively. As result, the body weight gain of the rats was decreased by medium and high doses of Pu-erh tea treatments. Furthermore, the levels of serum total cholesterol (TC), triglyceride (TG) and atherosclerosis index (AI) were significantly lowered by Pu-erh tea compared to the control group. Conversely, high density lipoproteincholesterol (HDL-C) level of the rats was significantly elevated by Pu-erh tea treatments. In addition, Pu-erh tea treatments increased the activities of anti-oxidative enzymes such as superoxide dismutase (SOD) and glutathione peroxides (GSH-Px), whereas reduced the level of lipid peroxidation product malondialdehyde (MDA) in obese rats. Collectively, our find-ings revealed that Pu-erh tea exerts comprehensive benefits in anti-obesity, anti-atherosclerotic and anti-oxidant effects, therefore can be used as a promising functional food in obesity management.

Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice

Objective:To evaluate possible lipid catabolism and body fat regulation effects of 3-caffeoylquinic acid in Green coffee bean extract(GCBE) in high-fat diet(HFD)-induced obese mice.Methods:Obesity was induced in mice using a HFD for four weeks.Then,mice were fed only HFD or HFD with GCBE at 50,100,and 200 mg/kg.Fatty acid synthesis mechanism regulation of body fat was investigated through real-time PCR and Western blot assay.Body fat reduction was measured through dual-energy X-ray absorptiometry.Results:In HFD-induced obese mice,GCBE treatment significantly decreased body weight gain,liver weight and white adipose tissue weights with regulation of adipose tissue lipolysis hormones,like adiponectin and leptin.GCBE treatment decreased mR NA expression levels of adipogenesis and adipocyte metabolism related genes in adipose tissues and the liver,and decreased the corresponding protein expression.Dual energy X-ray absorptiometry measurements were used to compare body fat between mice on high-fat and those treated with GCBE.GCBE treated mice had a lower fat mass compared to HFD alone fed mice and relative body weight and fat mass were markedly decreased.Conclusions:GCBE has a potential anti-obesity effect with lowering body fat accumulation by regulating adipogenesis and lipid metabolism-related genes and proteins in WAT and liver.

Rhinacanthus nasutus leaf improves metabolic abnormalities in high-fat diet-induced obese mice

Objective:To investigate the effect of Rhinacanthus nasutus(R.nasutus) leaf extract on impaired glucose and lipid metabolism in obese ICR mice.Methods:Obesity was induced in the male ICR mice by feeding them a high-fat diet(60 kcal%fat) for 12 weeks.After the first six weeks of the diet,the obese mice were administered with the water extract of R.nasutus leaves at 250 and 500 mg/kg per day for the next six weeks.Subsequently,the blood glucose,lipid profiles,insulin,leptin,and adiponectin levels were measured.The liver and adipose tissues were excised for histopathological examination and protein expression study.Results:After six weeks of the treatment,R.nasutus extract(at 250 and 500 mg/kg per day) was found to reduce the elevated blood glucose level,improve the insulin sensitivity,decrease the serum leptin,and increase the serum adiponectin levels.The obese mice treated with R.nasutus were found to have a reduction in the increased lipid concentrations in their serum and liver tissues.Moreover,treatment with R.nasutus reduced the fat accumulation in the liver and the large adipocyte size in the fat tissues.Interestingly,the administration with R.nasutus extract was marked by an increase in the hepatic peroxisome proliferators-activated receptor alpha,fat cell adiponectin,and glucose transporter 4 proteins.Conclusions:To the best of our knowledge,the present study is the first report on the impact of R.nasutus extract in improving the impaired glucose and lipid metabolism in high-fat diet-induced obesity in mice via stimulating the insulin sensitivity in the liver and adipose tissues.

Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet-induced obese rats

Aim： To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 （PDE5） inhibitor, on penile erection in obese rats. Methods： The rats were fed a high-energy diet for 12 weeks and divided into three groups： an obesity-resistant （OR） control group, an obesity-prone （OP） control group, and an OP-DA-8159 treatment （DA-8159） group. The electrostimulation-induced erectile responses were measured in all groups. The body weight, plasma cholesterol, triglyceride and glucose levels were also measured. Results： In the OP control group, the maximum intracavernous pressure （ICP） and ICP/blood pressure （ICP/BP） ratio after electric stimulation were significantly lower than those in OR control group. The corresponding area under the curve （AUC） of the ICP/BP ratio, the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group, but this difference was not significant. The body weight gain, plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159, a significant increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding AUCs in the DA-8159 group were also higher than those in the two control groups. Furthermore, the detumescence time was significantly prolonged after treatment with DA-8159. Conclusion： These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction （ED） can be improved by the treatment with DA-8159, indicating DA-8159 might be a treatment option for ED associated with obesity.

Anti-lipogenic effect of Senna alata leaf extract in high-fat diet-induced obese mice

Objective: To examine the effect of Senna alata(S. alata) leaf extracts on the regulation of lipid metabolism in high-fat diet-induced obese mice.Methods: The obesity condition was induced in the male ICR mice by feeding them with high-fat diet(45 kcal% fat) for 12 weeks. At the 7th week of diet feeding, the obese mice were treated with the water extract of S. alata leaf at 250 and 500 mg/kg/day, respectively, that continued for six weeks. At the end of the treatment period, the biochemical parameters were determined. The hepatic histology and the gene and protein expressions were also examined.Results: In comparison with the obese control mice, the mice treated with S. alata showed a significant reduction in the elevated blood glucose levels and a decrease in the serum insulin and leptin levels. A reduction in the serum total cholesterol, triglyceride,non-esterified fatty acid, and hepatic triglyceride levels were also observed. The histological examination of the obese mice treated with S. alata showed a reduced lipid accumulation in the liver tissue. Hepatic lipogenic gene expression showed that S. alata decreased the activity of sterol regulatory element binding protein 1c, fatty acid synthase,and acetyl-Co A carboxylase. S. alata could suppress hepatic peroxisome proliferatoractivated receptor gamma(PPARg) protein. Moreover, the protein expression of PPARa in liver tissue was clearly increased by S. alata treatment.Conclusion: The treatment with S. alata could decrease several parameters of impaired lipid metabolism in the obese mice by downregulating sterol regulatory element binding protein 1c and PPARg and upregulating PPARa. This study is the first report on the role of S. alata leaf extract in alleviating the abnormal lipid metabolism in obese conditions.

Ethanolic extract of cashew apple inhibits lipid metabolism and ameliorates obesity in atherogenic diet-induced obese rats

Objective:To evaluate the anti-obesity activity of ethanolic extract of cashew apple using various in vitro and in vivo models.Methods:Phytochemical screening was carried out in ethanolic extract of cashew apple,followed by quantification of phenol and flavonoid.Antioxidant potential was evaluated using 2,2-diphenyl-1-picrylhydrazyl and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)scavenging assays.The inhibitory effect of ethanolic extract of cashew apple on atic lipase was also studied.In addition,anti-obesity activity was determα-amylase and pancreined in two in vivo models,lipid emulsion model and atherogenic diet-induced obese rat model.Levels of postprandial plasma triglycerides were assessed in lipid emulsion model,whereas serum lipid profile,in vivo antioxidants and histopathological studies of the carotid artery and liver were performed in an atherogenic diet-induced obese model.Results:Phytochemical screening revealed the presence of carbohydrates,alkaloids,polyphenols,terpenoids,and steroids.The in vitro assays showed inhibition of otential.Ethanolic extract of cashew appα-amylase and pancreatic lipase and strong antioxidant ple showed significant and timedependent inhibitory activity on postprandial triglycerides after administration of lipid emulsion for 5 h.Ethanolic extract of cashew apple at 200 and 400 mg/kg on day 60 showed a significant reduction in body weight,body mass index and atherogenic index,whereas lipid profile and liver function marker levels in the serum were decreased in a dose-dependent manner at time intervals(day 0,20,40,and 60)compared to the atherogenic diet-induced obese rats.Histological observations showed reduced non-alcoholic fatty liver deposits and decreased atherosclerotic fatty streak plaques(carotid artery)after treatment with ethanolic extract of cashew apple.Conclusions:Ethanolic extract of cashew apple ameliorates obesity,which may be partly mediated by its delayed absorption of cholesterol and carbohydrates.

The Role of β3-adrenergic Receptor Gene in Neuropeptide Y Y5Receptor Antisense Gene Therapy of Diet-induced Obese Rats

Objective: To study the role of β3-adrenergic receptor gene in neuropeptide Y(NPY) Y5 receptor antisense gene therapy of diet-induced obese rats.Methods: The diet-induced obese rats were prepared by feeding a high-nutrition diet. Lateral ventricular was cannulated in obese rats which then received an intraventricular injection of either 5 μg/μl NPY Y5 receptor antisense or 10 μl missense oligodeoxynucleotide or saline of 10 μl respectively in every rat. When the rats were killed, the wet weight of abdominal adipose tissue, the level of serum lipid and lipoprotein were measured. Total RNA from the retroperitoneal adipose tissue was extracted and the level of β3-adrenergic receptor gene mRNA expression was evaluated by RT-PCR.Results: ①The wet weight of abdominal adipose tissue, the levels of serum lipids were greatly higher in diet-induced obese rats than those in normal rats. However, there were much lower β3-adrenergic receptor gene mRNA expression levels in retroperitoneal adipose tissue in diet-induced obese rats as compared with those in normal rats. ②After the diet-induced obese rats were intraventricularly administered with NPY Y5 receptor antisense oligodeoxynucleotide, the levels of β3-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue of diet-induced obese rats were strikingly up-regulated, whereas the wet weight of abdominal adipose tissue, the levels of serum lipids were markedly reduced.Conclusion: Intraventricular administration of antisense oligodeoxynucleotide to NPY Y5 receptor could significantly reduce the abdominal adipose tissue and the levels of serum lipids in diet-induced obese rats by up-regulating the level of β3-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue.

Anti-insulin resistant effect of ferulic acid on high fat diet-induced obese mice

Objective: To evaluate the insulin sensitivity action of ferulic acid(FA) in skeletal muscle and hypothalamus of high-fat diet(HFD)-induced obese mice. Methods: Obese mouse model was induced by HFD(45 kcal% lard fat) for 16 weeks. After 8 weeks of HFD feeding, these obese mice were orally treated with FA at doses of 25 and 50 mg/kg/day for 8 weeks. At the end of all treatments, the epididymal fat, pancreas, skeletal muscle and hypothalamus were removed for biochemical parameter and protein expression examinations. Results: FA treatment significantly decreased leptin level in fat tissue and insulin level in pancreas(P < 0.05). Interestingly, obese mice treated with FA increased the protein expressions of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and phosphorylated-protein kinase B in both muscle and brain(P < 0.05). The phosphorylations of adenosine monophosphate-activated protein kinase and acetyl-CoA carboxylase in muscle, and leptin receptor protein in hypothalamus were also increased(P < 0.05). The pancreatic islets histology showed smaller size in obese mice treated with FA compared to untreated obese mice. Conclusions: These findings indicate the beneficial effect of FA in improving insulin resistance in HFD-induced obese mice. These effects are probably mediated via modulating the insulin receptor substrate/phosphatidylinositol 3-kinase/protein kinase B or adenosine monophosphate-activated protein kinase pathways.

Long-Term Treatment with an Herbal Formula MCC Ameliorates Obesity-Associated Metabolic Dysfunction in High Fat Diet-Induced Obese Mice: A Comparative Study among MCC and Various Combinations of Its Constituents

Obesity has been found to be associated with increased incidence of various metabolic disorders. Anti-obesity interventions are therefore urgently needed. An earlier study has demonstrated that treatment with an herbal formula MCC, which comprises the fruit of Momordica charantia (MC), the pericarpium of Citri reticulate (CR) and L-carnitine (CA), reduced the weight gain in high fat diet (HFD)-fed mice. In the present study, we investigated the effect of long-term treatment with MCC (6 g/kg/day × 40 doses) and various combinations of its constituents in HFD-fed female ICR mice. Body weight change was monitored during the course of the experiment. Total and differential adiposity, plasma lipid contents, metabolic enzyme activities and mitochondrial coupling efficiency in skeletal muscle were measured. Glucose homeostasis was also assessed. Results showed that HFD increased the body weight, total and differential adiposity, and plasma lipid contents as well as impaired metabolic status in skeletal muscle and glucose homeostasis. MCC and all combinations of its constituents reduced the weight gain in HFD-fed mice, which was accompanied with an improvement on glucose homeostasis. While MC, CA and CR independently suppressed the HFD-induced weight gain in mice, MC seems to be the most effective in weight reduction, all of which correlated with the induction of mitochondrial uncoupling in skeletal muscle. Only CA and CR, but not MC, significantly reduced the total adiposity and visceral adiposity as well as plasma cholesterol level. However, the two component combinations, MC + CR and MC + CA, decreased the degree of visceral adiposity and plasma cholesterol level, respectively. MCC treatment at 1.5 g/kg (but not a higher dose of 6 g/kg) suppressed visceral adiposity and induced mitochondrial uncoupling in skeletal muscle in HFD-fed mice. The finding suggests that MCC may offer a promising prospect for ameliorating the diet-induced obesity and metabolic disorders in humans.

Effects of Siraitia grosvenorii extracts on high fat diet-induced obese mice:a comparison with artificial sweetener aspartame

Long-term artificial sweetener intake is linked to increased risk of obesity. In the present study, supplement of natural sweetener from Siraitia grosvenorii(SG)(or Momordica grosvenorii) fruit, compared with the artificial sweetener aspartame(ASM), was evaluated for anti-obesity effects on mice fed with high fat diet(HFD). We found that, in contrary to ASM, SG extracts prevented body weight gain, the insulin resistance and fat mass accumulation in HFD mice. SG extracts treatment inhibited the infiltration of inflammatory macrophages and lowered the levels of the fat inflammatory cytokines(leptin, macrophage chemoattractant protein 1(MCP-1) and tumor necrosis factor-α(TNF-α)) in adipose tissues. In addition, SG extracts supplement counteracted the remodeling of gut microbiota resulted from HFD. However, ASM supplement aggravated the HFD-induced obese performances, fat inflammation and dysregulation of gut microbiota. Taken together, our results indicate that supplement of SG extracts may represent a promising alternation of artificial sweeteners in preventing metabolic diseases.

Effect of Thunbergia laurifolia water extracts on hepatic insulin resistance in high-fat diet-induced obese mice

Objective:To examine the effect of water extract of Thunbergia laurifolia on hepatic insulin resistance in high-fat diet-induced obese mice.Methods:High-fat diet with 45 kcal%lard fat was used for obesity induction in ICR mice.The mice were fed with high-fat diet for 16 weeks,and during the last 8 weeks,they were treated with 200 mg/kg/day of water extracts from Thunbergia laurifolia leaf,stem and flower.Serum biochemistry,liver histology,and protein expression were examined after the treatment.Results:Extracts from all of the three parts of Thunbergia laurifolia significantly alleviated hyperglycemia,hyperlipidemia,hyperinsulinemia,and hyperleptinemia.The stem and flower extracts improved glucose tolerance.All of the extracts significantly reduced serum TNFαand monocyte chemoattractant protein-1 levels.Liver weight,triglyceride levels,and lipid accumulation were also decreased.Moreover,hepatic glucose-6-phosphatase level was significantly decreased,while the levels of PPARα,phosphorylated AMPK,and phosphorylated Akt were significantly increased with treatment of Thunbergia laurifolia extracts.Conclusions:Thunbergia laurifolia extracts can ameliorate hepatic insulin resistance in high-fat diet-induced obese mice by improving glucose and lipid homeostasis,which may be associated with stimulating phosphorylation of AMPK and Akt pathways.

Pandanus amaryllifoliusleaf extract improves insulin sensitivity in high-fat diet-induced obese mice

OBJECTIVE To investigate the effect of Pandanus amaryllifolius leaf in high-fat diet-induced insulin resistance in mice model.METHODS To induce obesity,male ICR mice were fed with a high-fat diet(45%fat)for six weeks.The mice were divided into four groups(n=8):non-obese control mice were treated with 5% gum arabic and obese mice were treated with Pandanus amaryllifolius(125and 250mg·kg-1·d-1),or 5% gum arabic.After six weeks of treatments,the fasting blood glucose,serum insulin,OGTT and fat cell protein expression of glucose transporter 4(GLUT4)were determined.RESULTS Administration of Pandanus amaryllifolius showed significantly(P<0.05)reduced the high blood glucose,inhibited the abnormal increase in blood glucose level during OGTT,and decreased the high level of serum insulin.Moreover,it is interesting that the protein expression of GLUT4 was effectively increased by Pandanus amaryllifolius.CONCLUSION These findings demonstrate that the extract from Pandanus amaryllifolius leaf possesses antihyperglycemic action in obese mice by improving insulin sensitivity and stimulating GLUT4 expression in adipose tissue.

Effects of Brassica oleracea extract on impaired glucose and lipid homeostasis in highfat diet-induced obese mice

Objective: To examine the effect of Brassica oleracea extract(BO) on impaired glucose and lipid homeostasis in high-fat diet(HFD)-induced obese mice. Methods: Obesity of ICR mice was induced by feeding a HFD(45 kcal% lard fat) for 16 weeks. During the last 8 weeks of study period, obese mice were additionally administered with BO(100 and 200 mg/kg/day). The metabolic parameters were determined. The gene expressions of hepatic lipogenesis were also studied. Results: After 8 weeks of treatment, BO(100 and 200 mg/kg) significantly reduced hyperglycemia and improved insulin sensitivity(P < 0.05). The serum lipid(total cholesterol, triglyceride, and non-esterified fatty acid) and hepatic triglyceride and nonesterified fatty acid were decreased(P < 0.05). The levels of insulin and leptin in serum were also decreased(P < 0.05). Moreover, the expressions of hepatic lipogenic genes including sterol regulatory element-binding protein 1 c, fatty acid synthase, and acetyl-CoA carboxylase were decreased by BO treatment(P < 0.05). Conclusions: These results suggest that BO is a new therapeutic agent for improving the homeostasis of glucose and lipid in HFD-induced obese mice probably by suppression of lipogenic genes in liver tissue.

CORRELATIONS BETWEEN BLOOD PRESSURE AND BODY WEIGHT, SERUM LEPTIN IN HIGH CALORIE DIET-INDUCED OBESE RATS

Objective To examine the change of body weight (BW) and blood pressure (BP) in obese rats, clarify relationships between BP and BW and other factors. Methods Male Spraque-Dawley rats were fed either with normal diet (ND) or high calorie diet (HC) for 20 weeks. BW and BP of tail artery were observed biweekly and tetraweekly respectively; serum leptin and fasting insulin (FINS) were detected by enzyme-linked immunoadsordent assay (ELISA) and radioimmunoassay (RIA) respectively. Fasting plasma glucose (FPG) and free fatty acid(FFA) were measured by conventional means. Results BW, abdominal fat weight (AFW), ratio of abdominal fat weight to body weight (R_ F/W), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum levels of leptin and FINS, FPG, FFA increased in the HD group after 20 weeks diet intervention (P<0.05 or P<0.01). SBP was strongly correlated with BW, leptin, FINS and FFA (P<0.05), DBP was correlated with FFA (r=0.47, P<0.05). In addition, leptin was positively correlated with BW, AFW, R_ F/W, FINS and FFA (P<0.05 or P<0.01). Conclusion In this study of high calorie-diet induced rats, the gain of BW is accompanied by increased BP. The obese rats have hyperleptinemia, hyperinsulinemia, hyperglycemia and dyslipidemia which may have important effects on the development of obesity-related hypertension. R_ F/W is the key factor in which affect serum leptin level.

The effect of PPARδ agonists (HS00098) on serum lipid profiles in diet-induced obese rhesus monkeys

Aim Activation of peroxisome proliferator-activated receptor δ (PPARδ) subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. We aim to explore the effects of peroxisome proliferator-activated receptor δ (PPARδ) subtypes on serum lipid profiles in obese rhesus monkey, especially evaluate the efficacy of investigational new drug (HS00098). Methods: First, a prototype of obese rhesus monkey was established by continuously feeding test animals a high fat diet for 2 months. Fifteen obese rhesus monkeys were randomly divided into 3 groups, and the 2 test groups were treated with GW 501516 and HS00098. The test groups were administered doses of 0.3 mg/kg for 1 month, then with 1 mg/kg for 1 month, and finally with 3 mg/kg for 1 month. The control group received placebo treatment. In each experiment, the body weight of each animal was measured and recorded initially and prior to changing the dose of the drug each month. The total cholesterol, blood glucose, triglyceride, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum Apo-A1, Apo-B100 and insulin were tested. Results: The average body weight gain of the GW501516 and HS00098 groups was significantly lower than that of the control group. The group receiving the HS00098 treatment had a higher signifycant increase in high density lipoprotein and apo-A1 (P < 0.05) than the control monkeys, while the total cholesterol, triglycerides, low density lipoproteins, apo-B100, and insulin (P < 0.05 or P < 0.01) were significantly decreased. Compared with GW50-1516, the effects of HS00098 on serum lipid profiles in diet-induced obese rhesus monkeys are more obvious. Conclusion: These results suggested that the investigational drug (HS00098) can effectively reduce body weight, blood lipid and blood sugar levels of diet-induced obese rhesus monkeys.