• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.401-408
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• 2011

Type 2 diabetes mellitus (NIDDM) is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. In order to control the type 2 diabetes mellitus, anti-hyperglycemic effect of Triticum aestivum L. water extracts (TAWE) was investigated in 7 week old male diabetic C57BL6/J-ob/ob mice. For the experiments, the diabetic animal model ob/ob mice and non-diabetic animal model lean mice were divided into 3 groups: non-treatment control group (Control), and two experimental groups orally treated with 25 or 100 mg/kg/day dose of TAWE (TAWE-25 and TAWE-100, respectively). The lean mice were used as the non-diabetic normal control. TAWE was orally administrated for 6 weeks and the diabetic clinical markers, including blood glucose level, body weight, organs weight and insulin level were determined. The oral administration of TAWE-100 in ob/ob diabetic mice significantly decreased blood glucose level (78.4%) and body weight (11.9%) compared with diabetic control group. The weights of organs, including spleen, liver, kidneys, heart and lung were not different among groups, while the treatments of TAWE-100 in ob/ob diabetic mice significantly reduced blood total cholesterol (24.35%) and triglyceride (23.97%) levels compared with the diabetic control group. The levels of serum insulin and glucose tolerance were improved after TAWE-100 treatment in ob/ob diabetic mice. Moreover, the immunohistochemical staining for insulin detection in pancreatic islet $\beta$-cells expressed high level of insulin in TAWE-100 treated ob/ob mice. From the above results, the intake of TAWE may be effective in anti-hyperglycemia by the attenuation of glucose and lipid levels. TAWE-containing diets or drugs may be beneficial for controlling diabetes mellitus type 2 in human.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1163-1169
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• 2007

Effects of Sotosaja hwan on Blood Glucose, Hyperlipidemia, Polyol Pathway and Antioxidative Mechanism in ob/ob Mouse Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Sotosaja-hwan has been known to be effective for the antiaging and composed of four crude herbs. In male ob/ob mouse in severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activites and mechanisms of Sotosaja-hwan were examined. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. The effects of Sotosaja-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical $({\cdot}O_2)$, MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Sotosaja-hwan lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Sotosaja-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the generation of ${\cdot}O_2$ in the kidney. Finally, MDA+HAE levels was increased and GSH/GSSG ratio was decreased in the ob/ob mice, whereas those were improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan showed the antidiabetic and anti hyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.4
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• pp.333-339
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• 2014

Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver, glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters, hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly, Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.

• Journal of Veterinary Science
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• v.21 no.6
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• pp.91.1-91.15
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• 2020

Background: Sulforaphane (SFN) is an isothiocyanate compound present in cruciferous vegetables. Although the anti-inflammatory effects of SFN have been reported, the precise mechanism related to the inflammatory genes is poorly understood. Objectives: This study examined the relationship between the anti-inflammatory effects of SFN and the differential gene expression pattern in SFN treated ob/ob mice. Methods: Nitric oxide (NO) level was measured using a Griess assay. The inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels were analyzed by Western blot analysis. Pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RNA sequencing analysis was performed to evaluate the differential gene expression in the liver of ob/ob mice. Results: The SFN treatment significantly attenuated the iNOS and COX-2 expression levels and inhibited NO, TNF-α, IL-1β, and IL-6 production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA sequencing analysis showed that the expression levels of 28 genes related to inflammation were up-regulated (> 2-fold), and six genes were down-regulated (< 0.6-fold) in the control ob/ob mice compared to normal mice. In contrast, the gene expression levels were restored to the normal level by SFN. The protein-protein interaction (PPI) network showed that chemokine ligand (Cxcl14, Ccl1, Ccl3, Ccl4, Ccl17) and chemokine receptor (Ccr3, Cxcr1, Ccr10) were located in close proximity and formed a "functional cluster" in the middle of the network. Conclusions: The overall results suggest that SFN has a potent anti-inflammatory effect by normalizing the expression levels of the genes related to inflammation that were perturbed in ob/ob mice.

• Journal of Life Science
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• v.22 no.1
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• pp.1-6
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• 2012

The present study examined the effects of consumption of Jeju ground water containing vanadium components on oxidative stress in obese (ob/ob) mice. Intake of Jeju ground water decreased the generation of oxidative stress induced-lipid peroxidation in the liver of ob/ob mice It also enhanced the enzymatic antioxidant defense system by increasing the protein expression and activity of superoxide dismutase, catalase, and glutathione peroxidase in liver tissues. Jeju ground water intake also upregulated the intracellular content of reduced glutathione. The induction of antioxidant enzyme expression by consumption of Jeju ground water was mediated by the erythroid transcription factor NF-E2 (Nrf2). Increased nuclear expression of phospho Nrf2 was observed in ob/ob mouse liver cells following ntake of Jeju ground water. These results suggest that consumption of Jeju ground water stimulated the antioxidant defense system in the livers of ob/ob mice via induction of Nrf2.

• YAKHAK HOEJI
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• v.44 no.5
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• pp.391-398
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• 2000

Leptin, the product of the ob gene, is a small peptide molecule synthesized by white adipocytes with an important role in the regulation of body fat and food intake. Based on the evidence that synthesis of leptin is regulated by female sex hormone, estrogen, this present study was investigated whether sex hormone precursor DHEA, can regulate obese gene expression in lean and genetically obese (ob/ob) mice. Antiobesity activity of DHEA was evaluated by determining body weight, food consumption, epididymal fat weight and serum levels of cholesterol and triglyceride in ICR, C57BL/6J, and ob/ob mice. The treatment of C57BL/6J lean and obese mice with a diet containing 0.3% and 0.6% DHEA resulted in lowered rates of weight gain in comparison to non-treated mice, although much greater response was found in the obese mice. All other concentrations of DHEA (0.015%, 0.06%, 0.15%, 0.3%) except the highest one(0.6%) showed no significant effects on weight gain in ICR mice. Food consumption was significantly decreased in all mice treated with 0.6% DHEA, whereas it was not decreased in ICR mice at lower concentrations than 0.6% DHEA. DHEA decreased significantly epididymal adipose tissue weight and serum triglyceride levels dose dependently in lean and obese mice. However serum cholesterol levels were decreased at lower concentrations than 0.15% DHEA and increased at concentrations of 0.3% and 0.6% DHEA in lean and obese mice. These increases in serum cholestrol levels at high concentrations of DHEA might result from the fact that DHEA has a cholesterol moiety thereby interfered the assay system. As an approach to elucidate the mechanism for antiobesity activity of DHEA, we examined mRNA levels of obese gene in the adipocyte and obese gene product (leptin) in the serum. The results showed that DHEA did not affect obese gene expression in ICR and C57BL/6J mice. Therefore, we concluded that antiobesity activity of DHEA was not modulated by obese gene expression.

• The Journal of Internal Korean Medicine
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• v.39 no.4
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• pp.751-763
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• 2018

Objective: This study was undertaken to investigate how magnolia bark extract affects ob/ob mouse in terms of metabolic inflammation and insulin resistance. Methods: Leptin-deficient ob/ob mice were divided into 2 groups (n=5): a normal saline treatment (=control) and magnolia bark treatment. Wild type mice were the lean group (n=5). After 5 weeks, we measured fasting blood sugar (FBS) and conducted oral glucose tolerance tests (OGTTs) in each group. After 6 weeks, we measured body weight, epididymal fat pad weight, liver weight, serum glucose, serum insulin, and gene expression of tumor necrosis factor-${\alpha}$, interferon-${\gamma}$, and interleukin-6. We characterized the phenotype of adipose tissue macrophages (ATMs) and analyzed fractions of the phenotype in each group by flow cytometry. Results: In the magnolia bark group, fasting blood sugar, oral glucose tolerance levels, and insulin resistance (HOMA-IR) were significantly decreased. The population and proportion of ATMs among leukocytes in adipose tissue were significantly decreased in the magnolia bark group. The population and proportion of M1 type ATMs among ATMs were significantly decreased in the magnolia bark group. Gene expression of tumor necrosis factor-${\alpha}$ was significantly decreased in the magnolia bark group. Conclusions: These results support a positive effect of magnolia bark on metabolic diseases such as insulin resistance and metabolic inflammation in leptin-deficient ob/ob mice.

• The Journal of Korean Medicine
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• v.30 no.1
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• pp.51-63
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• 2009

Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

• Nutrition Research and Practice
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• v.8 no.2
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• pp.172-176
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• 2014

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. MATERIALS/METHODS: Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined. RESULTS: Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels. CONCLUSIONS: These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.306-311
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• 2005

Semisulospira libertine (SL) has been used as a folk medicine for quenching a thirst, hepatic fever and inflammation in oriental countries. Although SL has been anecdotally ascertained to ameliorate the hepatic diseases, there are no sufficient experimental evidences. The purpose of this study was to examine the effect of Bitam-S, in which SL is a main component, on non-alcoholic fatty liver disease manifested in C57BL/6J ob/ob mice. At 6 week old, the ob/ob mice were randomly divided into four groups; control and three treatment groups. The control mice was to receive a regular diet, and the treatment groups were fed a regular diet with either 250mg/kg, 500mg/kg of Bitam-S (BS250 and BS500) or 300mg/kg of metformin (MT300) for a 8-week period. Bitam-S exerted beneficial effects on lipid homeostasis in ob/ob mice that are not necessarily due to its ability to decrease food intake but its specific effects on hepatic lipogenesis related genes (SREBP1a, FAS and SCD-1). The combined effects of Bitam-S to reduce body weight and lipogenic gene expressions, and reduce the deposition of triglyceride in the liver are indicative of a marked improvement in obesity-related non-alcoholic fatty liver disease. Taken together, Bitam-S has potential as a treatment agent for non-alcoholic fatty liver disease and deserves clinical trial in the near future.