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 TNFα and 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.

To evaluate the renoprotective effect of umbelliferone in high-fat diet/streptozotocin-induced type 2 diabetic rats. Methods: We established a streptozotocin-induced type 2 diabetic model in male Wistar rats. The rats were fed with high-fat diet (45 kcal% lard fat) and injected with 35 mg/kg streptozotocin. Diabetic rats were treated with umbelliferone for 8 weeks. At the end of the experimental period, the serum and kidney were used for measuring biochemical parameters, protein expression and histological analysis. Results: After 8-week treatment, umbelliferone decreased fasting plasma glucose, concentrations of malondialdehyde and monocyte chemoattractant protein-1 in the plasma and tissues. It also significantly reduced serum creatinine, blood urea nitrogen, serum advanced glycation end products, as well as kidney weight in type 2 diabetic rats (P<0.05). Moreover, umbelliferone reduced the 24-h urine albumin, but increased 24-h urine creatinine excretion (P<0.05). In renal protein expression, umbelliferone decreased the levels of transforming growth factor-b1 and fibronectin while increasing the levels of superoxide dismutase and catalase (P<0.05). Renal histological examination revealed an enlarged glomerular size in diabetic rats, which was smaller in umbelliferone-treated diabetic rats. Conclusions: Umbelliferone alleviates renal dysfunction in diabetes via decreasing hyperglycemia, oxidative stress, inflammation and glycation.

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 non-esterified 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 1c, 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.

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.

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 his-topathological 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 concen-trations 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.

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 the 5th week of treatment, oral glucose tolerance test was conducted. After six weeks of treat-ment, 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.

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 the 5th 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.

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.

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-CoA carboxylase. S. alata could suppress hepatic peroxisome proliferator-activated receptor gamma (PPARγ) protein. Moreover, the protein expression of PPARα 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 PPARγ and upregulating PPARα. This study is the first report on the role of S. alata leaf extract in alleviating the abnormal lipid metabolism in obese conditions.

Although peroxisome proliferator receptor (PPAR)-alpha and PPAR-gamma agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-delta has not been fully investigated. In this study, we examined the effects of the PPAR-delta agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-delta agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-gamma coactivator (PGC)-1alpha gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-alpha and MCP-1 was also examined in supernatant of Raw264. 7 cell culture. To address the effects of GW0742 on insulin signaling, we performed in vitro study with AML12 mouse hepatocytes. Rats treated with GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty infiltration of the liver. In liver tissues, mRNA expressions of TNF-alpha, MCP-1, and PGC-1alpha were significantly decreased in diabetic rats treated with GW0742 compared to diabetic control rats. We also observed that GW0742 had inhibitory effects on palmitic acid-induced fatty accumulation and inflammatory markers in HepG2 and Raw264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-delta agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1alpha gene expression, and improvement of insulin signaling.
Animals ; Anti-Inflammatory Agents/*pharmacology/therapeutic use ; Blood Glucose ; Cytokines/genetics/metabolism ; Diabetes Mellitus/blood/immunology/metabolism ; Fatty Liver/blood/*drug therapy/immunology ; Glucose Tolerance Test ; Hep G2 Cells ; Humans ; Insulin Resistance ; Liver/metabolism ; Male ; PPAR delta/*agonists/metabolism ; Rats ; Rats, Long-Evans ; Thiazoles/*pharmacology/therapeutic use ; Triglycerides/metabolism