• The Korean journal of internal medicine
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• 제33권6호
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• pp.1210-1223
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• 2018

Background/Aims: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. Methods: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. Results: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. Conclusions: These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

• Journal of Ginseng Research
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• 제41권1호
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• pp.23-30
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• 2017

Background: Ginsenoside Rg1 is a class of steroid glycoside and triterpene saponin in Panax ginseng. Many studies suggest that Rg1 suppresses adipocyte differentiation in 3T3-L1. However, the detail molecular mechanism of Rg1 on adipogenesis in 3T3-L1 is still not fully understood. Methods: 3T3-L1 preadipocyte was used to evaluate the effect of Rg1 on adipocyte development in the differentiation in a stage-dependent manner in vitro. Oil Red O staining and Nile red staining were conducted to measure intracellular lipid accumulation and superoxide production, respectively. We analyzed the protein expression using Western blot in vitro. The zebrafish model was used to investigate whether Rg1 suppresses the early stage of fat accumulation in vivo. Results: Rg1 decreased lipid accumulation in early-stage differentiation of 3T3-L1 compared with intermediate and later stages of adipocyte differentiation. Rg1 dramatically increased CAAT/enhancer binding protein (C/EBP) homologous protein-10 (CHOP10) and subsequently reduced the $C/EBP{\beta}$ transcriptional activity that prohibited the initiation of adipogenic marker expression as well as triglyceride synthase. Rg1 decreased the expression of extracellular signal-regulated kinase 1/2 and glycogen synthase kinase $3{\beta}$, which are also essential for stimulating the expression of $CEBP{\beta}$. Rg1 also reduced reactive oxygen species production because of the downregulated protein level of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 4 (NOX4). While Rg1 increased the endogenous antioxidant enzymes, it also dramatically decreased the accumulation of lipid and triglyceride in high fat diet-induced obese zebrafish. Conclusion: We demonstrated that Rg1 suppresses early-stage differentiation via the activation of CHOP10 and attenuates fat accumulation in vivo. These results indicate that Rg1 might have the potential to reduce body fat accumulation in the early stage of obesity.

• 대한한의학방제학회지
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• 제22권1호
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• pp.167-176
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• 2014

Objectives : This study investigated the improvement effects of Gangjihwan (DF) and combination of Gangjihwan and Gamisochehwan (GSH) on nonalcoholic fatty liver disease in a high fat diet-induced obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into five groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and atorvastatin, DF, and DF+GSH groups given a high fat diet with atorvastatin (10 mg/kg), DF (40 mg/kg), and DF+GSH (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, blood lipid markers, ALT concentrations, liver weight and histology were examined. Results : 1. Body weight gain was significantly decreased in DF, DF+GSH and atorvastatin groups compared with control. The extent of decreases was eminent in DF+GSH group. 2. Circulating concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol were decreased in DF, DF+GSH and atorvastatin groups compared with control. The decreases were significant in DF+GSH and atorvastatin groups. 3. Liver weights were decreased in DF, DF+GSH and atorvastatin groups compared with control. In particular, liver weight was significantly reduced only in DF+GSH group. 4. Hepatic lipid accumulation was significantly decreased in DF, DF+GSH and atorvastatin groups compared with control, and the magnitude of which was more effective in DF+GSH group than in DF-only group. 5. Circulating ALT concentrations were decreased in DF, DF+GSH and atorvastatin compared with control, but ALS levels were significantly reduced only in DF+GSH group. Conclusions : In conclusion, these results suggest that DF decreases body weight gain, improves blood lipid metabolism, and reduces liver weight and hepatic lipid accumulation, contributing to the improvement of nonalcoholic fatty liver disease. In addition, these effects were more effective in DF+GSH combination group than in DF-only group.

• 대한한의학방제학회지
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• 제22권1호
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• pp.113-122
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• 2014

Objectives : This study investigated the improvement effects of Pakistani (DF-a) and Chinese Ephedra herba-containing Gangjihwan (DF-b) on nonalcoholic fatty liver disease in a high fat diet-induced obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into five groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and atorvastatin, DF-a, and DF-b groups given a high fat diet with atorvastatin (10 mg/kg), DF-a (80 mg/kg), and DF-b (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, blood lipid markers, ALT concentrations, liver weight and histology were examined. Results : 1. Body weight gain was significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control. The extent of decreases was eminent in DF-a group. 2. Circulating concentrations of total cholesterol and LDL-cholesterol were significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control. The decreases were most effective in atorvastatin group. 3. Liver weights were decreased in DF-a, DF-b, and atorvastatin groups compared with control. In particular, liver weight was significantly reduced in DF-b group. 4. Hepatic lipid accumulation was significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control, and the magnitude of which was most effective in DF-b group. 5. Circulating ALT concentrations were decreased in DF-a, DF-b, and atorvastatin groups compared with control, but ALS levels were significantly reduced only in DF-b group. Conclusions : In conclusion, these results suggest that DF-a and DF-b decrease body weight gain, improve blood lipid metabolism, and reduce liver weight and hepatic lipid accumulation, contributing to the improvement of nonalcoholic fatty liver disease. In addition, these effects were similar between Pakistani and Chinese Ephedra herba-containing Gangjihwan.

• The Korean Journal of Physiology and Pharmacology
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• 제25권3호
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• pp.177-187
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• 2021

Metabolic syndrome (MBS) is a widespread disease that has strongly related to unhealthy diet and low physical activity, which initiate more serious conditions such as obesity, cardiovascular diseases and type 2 diabetes mellitus. This study aimed to examine the therapeutic effects of morin, as one of the flavonoids constituents, which widely exists in many herbs and fruits, against some metabolic and hepatic manifestations observed in MBS rats and the feasible related mechanisms. MBS was induced in rats by high fructose diet feeding for 12 weeks. Morin (30 mg/kg) was administered orally to both normal and MBS rats for 4 weeks. Liver tissues were used for determination of liver index, hepatic expression of glucose transporter 2 (GLUT2) as well as both inflammatory and fibrotic markers. The fat/muscle ratio, metabolic parameters, systolic blood pressure, and oxidative stress markers were also determined. Our data confirmed that the administration of morin in fructose diet rats significantly reduced the elevated systolic blood pressure. The altered levels of metabolic parameters such as blood glucose, serum insulin, serum lipid profile, and oxidative stress markers were also reversed approximately to the normal values. In addition, morin treatment decreased liver index, serum liver enzyme activities, and fat/muscle ratio. Furthermore, morin relatively up-regulated GLUT2 expression, however, down-regulated NF-κB, TNF-α, and TGF-β expressions in the hepatic tissues. Here, we revealed that morin has an exquisite effect against metabolic disorders in the experimental model through, at least in part, antioxidant, anti-inflammatory, and anti-fibrotic mechanisms.

• Laboraroty Animal Research
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• 제34권4호
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• pp.288-294
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• 2018

A few clues about correlation between endoplasmic reticulum (ER) stress and mulberry (Morus alba) leaves were investigated in only the experimental autoimmune myocarditis and streptozotocin-induced diabetes. To investigate whether a novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) could suppress ER in fatty liver, alterations in the key parameters for ER stress response were measured in high fat diet (HFD)-induced obese C57L/6 mice treated with EMfC for 12 weeks. The area of adipocytes in the liver section were significantly decreased in the HFD+EMfC treated group as compared to the HFD+Vehicle treated group, while their level was higher in HFD+Vehicle treated group than No treated group. The level of the eukaryotic initiation factor 2 alpha ($eIF2{\alpha}$) and inositol-requiring enzyme 1 beta ($IRE1{\alpha}$) phosphorylation and CCAAT-enhancer-binding protein homologous protein (CHOP) expression were remarkably enhanced in the HFD+Vehicle treated group. However, their levels were restored in the HFD+EMfC treated group, although some differences were detected in the decrease rate. Similar recovery was observed on the ER stress-induced apoptosis. The level of Caspase-3, Bcl-2 and Bax were decreased in the HFD+EMfC and HFD+orlistat (OT) treated group compared to the HFD+Vehicle treated group. The results of the present study therefore provide first evidence that EMfC with the anti-obesity effects can be suppressed ER stress and ER stress-induced apoptosis in the hepatic steatosis of HFD-induced obesity model.

• Journal of Applied Biological Chemistry
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• 제64권4호
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• pp.383-389
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• 2021

비만은 숙주의 전신 염증 및 대사 기능 장애에 기여하는 장 상피 장벽 기능 저하와 관련이 있다. 한국의 전통 식품으로 식이섬유가 풍부한 콩 제품은 항염증 반응을 비롯한 다양한 생물학적 활성을 나타내어 왔으나 대장 건강에 대해서는 보고된 바가 없다. 본 연구에서는 고지방 식이(HFD)를 섭취한 비만 모델에서 콩(CSB)에 대한 장 건강 증진 효과를 조사하였다. SD 쥐에게 동물 실험 기간 동안 HFD 또는 10.6% CSB가 함유된 HFD (HFD + CSB)를 제공하였다. CSB의 섭취는 HFD로 유발된 체중과 지방 축적 증가를 현저하게 감소시켰다. 또한, CSB의 섭취는 대장 조직에서 HFD에 의해 감소된 밀착 결합 지표(ZO-1, Claudin-1 및 Occludin-1)의 mRNA 발현을 개선시켰다. 또한, 조직병리학적 평가에서도 CSB 섭취는 대장 조직에서 HFD에 의해 증가된 염증 세포 침윤과 대장 상피 조직 붕괴를 개선하는 것으로 나타났다. Genus 수준에서 HFD 섭취에 의해 Lactobacillus, Duncaniella, Alloprevotella 등 미생물 종의 abundance 차이는 확인되었으나, CSB 섭취로 인한 영향은 명확하게 나타나지 않았다. NMDS 분석에서 HFD 섭취에 의해 유의적인 장내미생물 생태 이동을 보여주었지만 CSB 섭취는 차이가 없었다. HFD와 CSB 간 유의적으로 차이가 나타나는 genera를 조사하기 위해 LEfSe를 수행한 결과, CSB는 Anaerotignum, Enterococcus, Clostridium sensu stricto 및 Escherichia/Shigella 속의 풍부함을 증가시킨 반면 Longicatena 및 Ligilactobacillus의 풍부함을 감소시켰다. 이러한 결과는 CSB 섭취는 긴밀한 접합 성분을 개선하여 HFD로 악화된 대장 건강을 개선하는 반면 장내미생물생태에 긍정적인 효과를 미치는지에 대해서는 명확하지 않았다.

• Journal of Nutrition and Health
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• 제52권6호
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• pp.529-539
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• 2019

본 연구에서는 달맞이순의 항산화 및 항비만효과를 확인하기 위하여 건달맞이순 50% 에탄올 추출물 (OLE)을 이용하여 4가지 방법으로 in vitro 항산화효과를 측정하였고, C57BL/6 마우스에게 고지방식이 (45%Kcal fat)를 14주 동안 섭취시켜 비만을 유도하면서 OLE를 경구 투여하여 항비만효과와 in vivo 항산화효과를 알아보았다. OLE의 DPPH 라디칼 소거능과 SOD 유사 활성을 측정한 결과 IC₅₀은 각각 26.2 ㎍/mL과 327.6 ㎍/mL이었으며, FRAP 측정 결과 100 ㎍/mL 농도에서 56.7 ㎍ AA eq./mL의 효능을 보였다. 또한, hUC-MSC 세포에 OLE (200 ㎍/mL)를 처리 한 결과 노화로 인하여 감소된 GSH 수준을 65.1% 증가시켰다. 한편, 마우스에게 고지방식이와 함께 OLE를 저수준 (50 mg/kg BW; OL50)과 고수준 (100 mg/kg BW; OL100)으로 경구 투여한 결과 체중증가량은 대조군에 비하여 각각 41.5%와 42.2% 감소하였고, 내장지방량은 각각 40.5%와 45.9% 감소하였으며, 부고환지방세포의 크기는 각각 33.1%와 35.3% 감소하여 매우 우수한 비만억제효과를 보였다 (p < 0.05). OLE의 경구 투여는 고지방식이 대조군에 비하여 혈중 렙틴 농도와 중성지방 농도를 유의하게 감소시켰고, 특히 OL100군에서는 동맥경화지수 및 혈중 MDA 농도도 유의하게 감소하였다 (p < 0.05). 마우스 지방조직에서 측정한 catalase와 SOD-1의 활성은 고지방식이섭취로 인하여 증가하였으나 OLE 경구 투여 시 유의하게 감소하였다 (p < 0.05). 또한, 부고환 지방에서 지방대사 관련 인자들의 mRNA 발현량을 RT-PCR로 측정한 결과 OLE의 경구 투여는 고지방식이 섭취로 인하여 증가하였던 렙틴, PPARγ와 FAS의 발현을 유의하게 감소시킨 반면 고지방식이 섭취로 감소되었던 아디포넥틴의 발현량은 유의하게 증가시켰다 (p < 0.05). 고지방식이로 인하여 증가하였던 CPT-1의 발현량은 OLE 투여시 감소되는 경향을 보였으며, SREBP-1c의 발현량은 실험군 간에 유의한 차이가 없었다. 이들 연구결과를 종합하면, in vitro 항산화효과가 우수한 OLE를 고지방식이로 유도된 비만 마우스에게 경구 투여하였을 때 체내 산화적 스트레스를 낮추고, 지방합성을 억제함으로써 체중과 내장 지방량의 증가를 억제시키는 항비만 효과를 나타내었다. 따라서, OLE는 항산화기능식품 또는 비만 및 비만관련 만성질환을 예방하는 기능성식품의 개발에 기능성 천연소재로 활용될 수 있으리라 기대된다.

• 한국식품영양과학회지
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• 제41권4호
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• pp.501-509
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• 2012

비알코올성 지방간은 인슐린저항성을 근간으로 하는 대사증후군의 원인으로 생각되고 있으며 최근 그 발병율이 증가하고 있다. 본 연구진은 기장 열수추출물을 식이에 첨가하여 고지방식에 의해 인위적으로 지방간을 유도한 마우스에게 섭취시킨 후 혈청 내 생물학적 수치와 간조직 검사를 통하여 비알코올성 지방간 억제 효과를 검토하였다. 그 결과, 식이섭취량은 차이가 없었으나 간조직 무게가 1% 및 2% 기장 열수추출물 첨가식이군에서 유의적으로 감소하였고(p<0.05) 간조직 내 지방 축적이 유의적으로 감소하였음을 확인하였다. 또한 기장 열수추출물 첨가식이군의 경우 고지방식 대조군에 비해 혈청 중성지방 및 총 콜레스테롤이 감소하였고(p<0.05), HDL과 HDL-/총 콜레스테롤의 비율이 유의적으로 증가하여(p<0.05) 혈액의 지질 조성이 개선되었음을 알 수 있었다. HOMA-IR 및 포도당 내성 검사 결과 2% 기장 열수추출물 첨가군의 경우 이들 모두 유의적으로 감소하여 고지방식에 의한 인슐린 저항성 및 당흡수 부전을 기장 열수추출물이 완화시켰다(p<0.05). 한편 간조직에서 지방산 대사와 관련된 인자들의 유전자 발현을 측정한 결과 지방산 합성에 관여하는 L-FABP와 SCD1은 2% 기장 열수추출물 섭취군에서 유의적으로 감소하였고(p<0.05) 지방산 산화와 관련된 $PPAR{\alpha}$는 1% 및 2% 기장 열수추출물 섭취군에서 모두 유의적으로 증가하였다(p<0.05). 이상의 혈청 및 조직의 생물학적 수치와 간조직 검사 결과를 미루어 볼 때 기장 열수추출물 첨가 식이는 고지방식이에 의해 유도된 마우스의 비알코올성 지방간 치유 혹은 예방에 긍정적으로 기여할 수 있음을 시사해 준다.

• 생명과학회지
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• 제24권8호
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• pp.827-836
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• 2014

서구화된 식습관의 변화와 편리한 생활에 따른 운동 부족, 유전적 요인, 심리적 요인 등이 복잡하게 얽히면서 비만이 꾸준히 증가하는 추세이다. 한편, 감귤류에는 carotenoid, coumarin, phenylpropanoid, limonoid 등 60여종의 생리활성 물질이 함유되어 있으며 감귤박에는 bioflavonoid, carotenoid, hesperidin, terpenes 등이 풍부하게 함유되어 있다. 감귤박은 항산화 효과, 고혈압 예방, 혈중 LDL 콜레스테롤 함량 감소 효과 등이 있음이 보고되어 있고 최근 들어 감귤박의 비만을 억제하는 효능이 밝혀져 항비만 효과가 입증되었다. 본 연구에서는 고지방식으로 유도한 비만모델 ICR 생쥐에서 Aspergillus oryzae로 발효한 감귤박의 증강된 항비만 효과를 확인하고자 하였다. 항비만 효과를 확인하기 위해 생쥐의 체중변화와 조직의 무게변화를 관찰하였고, 그룹별 혈청 지질 농도, 간 지질농도 및 동맥경화지수를 관찰하였다. 그 결과, 고지방식이 투여군(HFD)에 비해 감귤박 추출물 투여군(CP)과 감귤박 발효 추출물 투여군(CPA)은 체중 증가량과 증체율이 감소하였고, 혈청과 간의 total cholesterol (TG), triglyceride (TC) 함량이 현저히 감소하였다. 한편, 유익한 cholesterol로 알려진 high density lipoprotein cholesterol (HDL-C) 함량은 일반식이 투여군(NFD)과 CPA 투여군이 비슷하였다. CP 투여군과 CPA 투여군의 조직 무게에서도 HFD 투여군보다 감소하여, 전체적으로 CPA 투여군에서 특히 유의적으로 감소하였다.