• Journal of Applied Biological Chemistry
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• v.66
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• pp.311-319
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• 2023

Caveolin-1 (Cav-1) is the main structural component of the caveolae on the plasma membrane, which regulates various cellular processes, including cell growth, differentiation, and endocytosis. Although a recent study demonstrated that Cav-1 might be involved in diabetes-associated inflammation, its exact role in the intestine was unclear. In this study, we examined the intestinal expression of Cav-1 in diabetic conditions. We also investigated its effect on lipopolysaccharide (LPS)-induced inflammation by expressing this protein in human intestinal Caco-2 cells lacking Cav-1. We observed that increased Cav-1 levels and decreased expression of tight junction proteins affected intestinal permeability in high-fat diet-induced diabetic mice. When Caco-2 cells were treated with LPS, Cav-1 enhanced the NF-κB signaling. Moreover, LPS reduced the expression of tight junction proteins while it increased cell-cell permeability and reactive oxygen species generation in Caco-2 cells and this effect was amplified by cav-1 overexpression. LPS treatment promoted phosphorylation of tyrosine-14 (Y14) on Cav-1, and the LPS-induced NF-κB signaling was suppressed in cells expressing non-phosphorylatable Cav-1 (tyrosine-14 to phenylalanine mutant), which reduced intestinal barrier permeability. These results suggest that Cav-1 expression promotes LPS-induced inflammation in Caco-2 cells, and phosphorylation of Y14 on Cav-1 might contribute to the anti-inflammatory response in LPS-induced NF-κB signaling and cell permeability.

• Natural Product Sciences
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• v.14 no.4
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• pp.215-220
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• 2008

Hypolipidemic effect of Insamsansa-eum (ISE, Ren-Shen-Shan-Zah-Yin in Chinese) consisted of Red ginseng (RG; the steamed root of Panax ginseng C.A. Meyer) and Crataegii fructus (CF, the fruit of Crataegus pinnatifida BGE) is used frequently in China and Korea as a herbal medicine to treat arteriosclerosis, was investigated. Treatment of ISE significantly reduced blood triglyceride (TG) and total cholesterol (TC) levels in Triton WR-1339-induced hyperlipidemic mice and serum TG levels in corn oil-induced hypertriglyceridemic mice. ISE significantly lowered the high blood TG and TC levels as well as body and epididymal mass weights in hyperlipidemic mice induced by long-term feeding of a high-fat diet and increased blood HDL cholesterol level. ISE and its ingredients, RG and CF, inhibited pancreatic lipase and HMG-CoA reductase activities. Of its ingredients, RG reduced the blood TC level and HMG-CoA reductase activity more than CF. CF reduced blood TG level and pancreatic lipase activity more than RG. These finding suggest that the antihyperlipidemic effect of ISE may be due to synergistic inhibition of HMG-CoA reductase and pancreatic lipase by RG and CF, and that ISE may be effective hypolipidemic agents.

• BMB Reports
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• v.55 no.11
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• pp.559-564
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• 2022

Diabetes mellitus is one of the most prevalent diseases in modern society. Many complicationssuch as hepatic cirrhosis, neuropathy, cardiac infarction, and so on are associated with diabetes. Although a relationship between diabetes and hair loss has been recently reported, the treatment of diabetic hair loss by Wnt/β-catenin activators has not been achieved yet. In this study, we found that the depilation-induced anagen phase was delayed in both db/db mice and high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice. In diabetic mice, both hair regrowth and wound-induced hair follicle neogenesis (WIHN) were reduced because of suppression of Wnt/β-catenin signaling and decreased proliferation of hair follicle cells. We identified that KY19382, a small molecule that activates Wnt/β-catenin signaling, restored the capabilities of regrowth and WIHN in diabetic mice. The Wnt/β-catenin signaling activator also increased the length of the human hair follicle which was decreased under high glucose culture conditions. Overall, the diabetic condition reduced both hair regrowth and regeneration with suppression of the Wnt/β-catenin signaling pathway. Consequently, the usage of Wnt/β-catenin signaling activators could be a potential strategy to treat diabetes-induced alopecia patients.

• The Korean journal of internal medicine
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• v.33 no.6
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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 the Korean Society of Food Science and Nutrition
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• v.44 no.7
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• pp.953-960
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• 2015

This study evaluated the effects of Rubus coreanus Miq. oil on the plasma lipid profile of high fat diet (HFD)-induced obese mice. Animals were randomly divided into 4 groups (n=10). After completion of the 5-week experimental period, we measured bodyweight gain, food intake, adipose tissue mass, and plasma lipid profile. We also analyzed the activities of carnitine and superoxide dismutase (SOD) involved in ${\beta}$-oxidation and antioxidation, respectively. Our results show that HFD-induced weight gain in animals in the R. coreanus Miq. oil diet group (RCO) and corn oil diet group (CO) was significantly lower compared to animals in the HFD group; RCO supplementation had a more noticeable effect than CO. Visceral and back fat weights were lower in the RCO and CO groups while plasma HDL cholesterol (HDL-C) and HDL-C per total cholesterol [HDL-C/TC (%)] ratio were significantly higher in the RCO group. The contents of acid-soluble acylcarnitine and total carnitine as well as SOD activation were significantly higher in the RCO group, but no significant difference was observed between the RCO and CO groups. In conclusion, RCO effectively averted elevation of total body weight and fat weight in HFD-induced obese mice and promoted increased HDL-C. Therefore, R. coreanus Miq. oil might play an anti-obesity role in obese people and could be used as an effective oil supplement.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.6
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• pp.667-673
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• 2009

The antihyperlipidemic and glycemic control effects of mycelia of Inonotus obliquus including protein-bound polysaccharides extract were investigated. In high fat diet-induced obese C57BL/6J mice, the mycelia of Inonotus obliquus including protein-bound polysaccharides extract showed significant decrease in epididymal fat tissue weight, blood triglyceride and VLDL level, triglyceride and total cholesterol level in liver, serum insulin and HOMA-IR level and AUC. Oral glucose tolerance test glucose level reduction were 4.9% (M150L; ${\beta}$-glucan 1.303 mg/kg bw), 9.5% (M150; ${\beta}$-glucan 2.606 mg/kg bw) after 180 min of glucose loading compared to H-C group. Besides, the mycelia of Inonotus obliquus including protein-bound polysaccharides extract treatment significantly increased glycogen contents in liver and adiponectin level in high fat diet-induced obese mice. In conclusion, the results showed that the mycelia of Inonotus obliquus including protein-bound polysaccharides extract possesses significant antihyperlipidemic and glycemic control effects in C57BL/6J mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.8
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• pp.910-918
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• 2017

Hyperlipidemia is known as a glucose and lipid metabolism-related disorder that is increasing in incidence in modern society. Red ginseng (RG) is a natural herb candidate with a positive effect on regulation of cholesterol and lipids. To observe the effects of RG on regulation of lipids, cholesterol, glucose, and oxidative stress, we examined the in vitro and in vivo effects of Chamdahan RG on differentiated 3T3-L1 adipocytes and high-fat diet-fed mice. RG ($50{\mu}g/mL$) significantly inhibited lipid synthesis in 3T3-L1 cells. In addition, a low concentration of RG (880 mg/kg/d) resulted in the lowest total blood cholesterol level. Moreover, high density lipoprotein-cholesterol quantity increased in RG-treated groups, consequently lowering the cardiovascular risk factor and atherosclerosis index. Moreover, RG increased activity of AMP-activated protein kinase, as a regulator of lipid and cholesterol synthesis, in adipose and liver tissues. Cumulatively, this paper suggests that RG has a positive effect on reducing the amounts of cholesterol and lipids and may be a good candidate for treating hyperlipidemia.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.4
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• pp.491-496
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• 2015

The purpose of this study was to assess the antioxidant, anti-inflammatory, and immuno-enhancing effects of Daebong persimmon (DP) and Bansi (BS) in vivo. Two types of astringent persimmons (DP and BS) were used for this experiment. C57BL/6J mice were assigned to the following groups: 1) lean control, 2) high-fat diet control (HF), 3) A region DP (3% wt/wt) with HF diet (A-DP), 4) B region DP with HF diet (B-DP), 5) C region DP with HF diet (C-DP), 6) D region BS with HF diet (D-BS), and 7) E region BS with HF diet (E-BS). All mice were sacrificed after 4 weeks of treatment, after which blood and tissues were collected. Antioxidant enzyme activities, inflammatory markers, and immune factors were evaluated. DP and BS treatments did not alter food intake or body weight, compared with HF. Administration of B-DP increased catalase activities in serum. Hepatic levels of malondialdehyde, a product of lipid peroxidation, were significantly lower in A-DP mice than in the HF group. A-DP had down-regulatory effects against inflammation induced by high-fat diet feeding, as shown by significant reduction of interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$. Additionally, A-DP treatment exerted an immuno-stimulatory effect, as shown by increasing levels of immunoglobulin G. DP treatment improved the level of insulin-like growth factor-1. These results indicate that DP has beneficial health effects on oxidative stress, inflammation, and immunity in vivo.

• Journal of Acupuncture Research
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• v.28 no.1
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• pp.1-14
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• 2011

목적 : 인진약침이 고지방식이로 유발된 비만 ICR mice에서 비만 및 동반 대사이상에 미치는 효과와 그 기전을 연구하고자 한다. 방법 : 인진약침의 비만 예방효과를 검증하기 위하여, 4주간 고지방식이를 급여하면서 150mg/kg 또는 300mg/kg의 인진약침을 양측 비수($BL_{20}$)에 교대로 매일 피하에 시술하였다. 또한 인진약침의 비만 치료효과를 검증하기 위하여, 4주간 고지방식이를 급여한 비만 ICR mice에 추가 4주간 고지방식이를 유지하면서 300 mg/kg 인진약침액과 vehicle control로써 등량의 distilled water를 양측 비수($BL_{20}$)에 교대로 매일 피하에 약침시술하였다. 인진약침의 항비만효과와 기전을 알아보기 위해, 체중, blood glucose, insulin, total cholesterol, triglyceride, non-esterified fatty acid (NEFA), AST, ALT levels 등 대사지표를 측정하고 부고환조직의 조직학적 관찰을 시행하였으며, AMPK activation과 adipocyte differentiation, fatty acid ${\beta}$-oxidation 및 thermogenesis와 관련된 gene expressions을 평가하였다. 결과 : 인진약침의 치료를 통하여 고지방식이 급여로 인한 체중의 증가가 억제되었을 뿐만 아니라, 비만 ICR mice의 체중을 감소시켰으며, glucose 및 lipid homeostasis를 개선시켰으며 지방조직의 증식을 억제하였다. AMPK의 phosphorylation과 CPT-1 및 UCP2의 발현을 증가시켰으며, PPAR-${\gamma}$, C/EBP${\alpha}$, aP2, LPL,FAS, SCD-1의 발현을 억제하였다. 결론 : 인진약침은 고지방식이 유도 동물모델에서 비만 및 동반 대사이상을 개선시키는 효과가 있으며, 이는 식이억제에 의한 2차적 효과라기 보다는 energy expenditure를 증가시키고, pre-adipocyte differentiation 및 proliferation을 억제하며, lipogenesis를 억제하고 lipolysis를 증가시키는 효과에 의한 것으로 사료된다.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.17 no.12
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• pp.2995-3000
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• 2013

We investigated the effects of testosterone on the improvement of white adipose tissue explant and its molecular mechanism in adipose tissue of high fat diet-fed male castrated (CAST) mice. The CAST mice treated with testosterone had lower adipose tissue weights, the average size of adipocytes and mRNA levels of $C/EBP{\alpha}$ as well as adipocyte marker genes than the vehicle-treated CAST mice. These results suggest that testosterone prevent the expression of $C/EBP{\alpha}$ and $C/EBP{\alpha}$-mediated adipocyte marker genes, resulting in decreased adipose tissue mass and adipocyte metabolism in male CAST mice. Moreover, this study give a valuable molecular and biological knowledge on testosterone therapy in obese hypogonadal men.