• 한국식품영양과학회지
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• 제40권3호
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• pp.401-408
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• 2011

본 연구에서는 소맥엽 물추출물을 제2형 당뇨동물모델 ob/ob 마우스에게 6주간 경구투여 하여 혈중 포도당 및 혈중 지질에 미치는 영향에 대하여 연구하였다. TAWE를 투여한 결과, lean 마우스 대조군 및 실험군들의 혈중 포도당 농도와 체중은 유의적인 변화가 없었다. 반면, ob/ob 마우스에서 대조군은 실험기간 내내 혈중 포도당 농도 및 체중이 높은 증가율을 보였으나, TAWE를 투여한 ob/ob 마우스에서는 혈중 포도당 및 체중 증가가 TAWE 투여용량 의존적으로 감소되었으며, 특히 TAWE-100 투여군에서 대조군에 비하여 체중 약 11.9%, 혈중 포도당 약 78.4% 감소되는 효과를 보였다. 또한 TAWE 투여가 실험동물의 장기무게에 미치는 영향을 알아보기 위해 비장, 신장, 심장 및 폐의 무게를 측정한 결과, lean 마우스 및 ob/ob 마우스 실험군 사이에 각각의 장기에 대한 유의적인 무게 차이는 나타나지 않았다. 혈중 인슐린 농도는 lean 마우스 대조군 및 실험군의 평균 농도(3.93 ng/mL)에 비하여 ob/ob 마우스 대조군(15.60 ng/mL), TAWE-100 투여군(20.19 ng/mL) 및 TAWE-25 투여군(19.66 ng/mL)에서 모두 높게 나타나는 경향을 보였지만 ob/ob 마우스 TAWE-100 투여군에서는 보다 증가된 인슐린 수치를 확인하였으며, 면역조직화학염색 시험법에서도 췌장 $\beta$세포의 인슐린 발현정도가 TAWE-100 투여군에서 가장 높게 나타났다. TAWE는 lean 마우스의 총콜레스테롤, 중성지방 및 HDL에 유의적인 영향을 미치지 않았지만, ob/ob 마우스 TAWE-100 투여군에서 대조군에 비해 총콜레스테롤 24.35%, 중성지방 23.97%가 감소하였고, HDL은 29.80% 증가하였다. 포도당 내당능에 대한 평가를 위해 당부하 검사를 실시한 결과 ob/ob 마우스 TAWE-100 투여군에서 60분부터 당부하가 유의적으로 개선되는 효과를 보였다. 결과적으로, TAWE의 인슐린 저항성 제2형 당뇨병 동물모델 ob/ob 마우스에 6주간의 장기투여는 혈당 및 혈중 지질대사를 개선할 수 있음을 의미하며, 임상학적 당뇨 증상완화 및 당뇨 합병증 예방 및 치료제로 음용할 수 있을 것으로 사료된다.

• 동의생리병리학회지
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• 제21권5호
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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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• 제18권4호
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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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• 제21권6호
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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.

• 생명과학회지
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• 제22권1호
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• pp.1-6
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• 2012

비만 마우스의 산화적 스트레스에 대해 바나듐 함유 제주 지하수에 대한 연구로서, 제주 지하수는 수도수 처리군보다 비만 마우스 간의 과산화 지질을 감소시켰으며, superoxide dismutase, catalase, 그리고 glutathione peroxidase의 단백질 발현 및 활성 그리고 환원형 glutathione 양을 증가 시켰다. 제주 지하수는 항산화 효소의 전사 인자인 erythroid transcription factor NF-E2 (Nrf2)의 인산화형 단백질 발현을 증가시켰다. 이로서 제주 지하수는 Nrf2의 활성화를 통하여 항산화 효소시스템을 증가시켰다.

• 약학회지
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• 제44권5호
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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.

• 대한한방내과학회지
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• 제39권4호
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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.

• 대한한의학회지
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• 제30권1호
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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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• 제8권2호
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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.

• 약학회지
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• 제49권4호
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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.