• Natural Product Sciences
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• 제19권4호
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• pp.316-323
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• 2013

Adipose tissue-derived chronic inflammation contributes to development of insulin resistance in obesity, leading to type 2 diabetes and cardiovascular disease. Baicalin, a flavonoid, has antioxidant, anti-inflammatory, antihyperglycemic, anti-adipogenic, and antiobesity effects. However, whether baicalin attenuates adipose tissue-derived development of insulin resistance remains still unclear. This study was to investigate effect of baicalin on the inflammatory changes involved in the development of insulin resistance in adipose tissue. RAW 264.7 cells and differentiated 3T3-L1 adipocytes were pretreated with various concentrations of baicalin in complete media for 1 h and then cultured in the presence or absence of LPS or TNF-${\alpha}$. Our results demonstrated that baicalin remarkably inhibited LPS-induced production of TNF-${\alpha}$, IL-6, and NO by RAW 264.7 cells in a dose-dependent manner. Baicalin also inhibited TNF-${\alpha}$-induced production of IL-6 and $PGE_2$ in differentiated 3T3-L1 cells in a dose-dependent manner, while upregulated TNF-${\alpha}$-suppressed expression of adiponectin and PPAR-${\gamma}$ mRNA and IRS-1 protein. These findings suggest that baicalin may prevent the adipose tissue-derived development of insulin resistance in obesity.

• 대한의용생체공학회:의공학회지
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• 제39권4호
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• pp.168-174
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• 2018

Adipocytes affect obesity through the regulation of lipid metabolism. Physical loading is an important regulator of fat tissue. There are ongoing in vitro studies inducing mechanotransduction on 3T3-L1 preadipocytes with mechanical stimulus in order to treat obesity by inhibiting adipogenesis and provoking cell death. In this study, our goal was to suggest a new therapy for obesity by investigating whether fluid shear stress (FSS) changes transcription factors on 3T3-L1 related with adipogenesis and cell death. FSS loading was applied to 3T3-L1 preadipocytes at 1Pa and 1Hz. After loading, bright field images were taken and an immunofluorescence assay was conducted to observe actin stress fiber formation. Western blot analysis was conducted to identify the activation of the ERK pathway as well as the adipogenic factors, which including C/EBPs and $PPAR{\gamma}$. The expression of osteopontin, a protein related to inflammation in adipose tissue, and cell death related factors, Bax, Bcl-2, and Beclin, were also measured. Results showed that FSS stimulated the formation of actin stress fibers in 3T3-L1 and also that the activation of C/EBPs decreased significantly when compared with the control group. $PPAR{\gamma}$ activation in the 2 hour FSS group was lower than the 1 hour FSS group, which implied that the results were time dependent. Additionally, there were no differences in the expression of cell death factors after FSS loading. In summary, similar to other fibroblasts, the formation of actin stress fibers induced by mechanotransduction may affect the differentiation of 3T3-L1, leading to inhibition of adipogenesis and inflammation.

• 대한한방소아과학회지
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• 제32권2호
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• pp.1-10
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• 2018

Objectives This study investigated the effects of Hataedock treatment with Douchi on induction of allergic rhinitis in obese induced NC/Nga mice. Methods NC/Nga mice were divided into control group (Ctrl), allergic rhinitis induced obese mice group (ARE), and allergic rhinitis induced obese mice group with Douchi Hataedock treatment (FGT). The 3-week-old mice of the FGT group were given one 10 mg/kg dose of Douchi Hataedock extract and sensitized with allergic antigens at weeks 4, 5, and 6. After 1 week of final sensitization, allergic rhinitis was induced primarily in mice nasal cavities for five days. After one week of the completion with the first induction, the second induction was introduced by the same method. After 1 week, few samples of the nasal mucosal tissues of each group were prepared. The factor of Th2 differentiation and inflammation control such that IL-4, STAT6, CD40, $Fc{\varepsilon}RI$, substance P, MMP-9, $NF-{\kappa}B$ p65, p-IkB, iNOS and COX-2 were observed by immunohistochemistry. Also, the difference in nasal mucosal injury was observed by histochemical method (PAS staining). Results The FGT group showed that reduced IL-4 production, STAT6 expression and CD40 expression by regulating excessive Th2 differentiation. Also, production of substance P and MMP-9 and activity of $Fc{\varepsilon}RI$ in mast cells were decreased. Inhibition of $NF-{\kappa}B$ p65 activity was induced by inhibition of p-IkB, and the production of inflammatory enzymes iNOS and COX-2 were decreased. In addition, the damage of intramural respiratory epithelium was low and excessive mucin secretion in goblet cells was low. Conclusions This study confirmed the possibility of controlling the allergic rhinitis in obese children who are expected to have an overactive inflammation.

• Nutrition Research and Practice
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• 제9권6호
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• pp.619-627
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• 2015

BACKGROUND/OBJECTIVES: Colitis is a serious health problem, and chronic obesity is associated with the progression of colitis. The aim of this study was to determine the effects of natural raw meal (NRM) on high-fat diet (HFD, 45%) and dextran sulfate sodium (DSS, 2% w/v)-induced colitis in C57BL/6J mice. MATERIALS/METHODS: Body weight, colon length, and colon weight-to-length ratio, were measured directly. Serum levels of obesity-related biomarkers, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), insulin, leptin, and adiponectin were determined using commercial kits. Serum levels of pro-inflammatory cytokines including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, and IL-6 were detected using a commercial ELISA kit. Histological study was performed using a hematoxylin and eosin (H&E) staining assay. Colonic mRNA expressions of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were determined by RT-PCR assay. RESULTS: Body weight and obesity-related biomarkers (TG, TC, LDL, HDL, insulin, leptin, and adiponectin) were regulated and obesity was prevented in NRM treated mice. NRM significantly suppressed colon shortening and reduced colon weight-to-length ratio in HFD+DSS induced colitis in C57BL/6J mice (P < 0.05). Histological observations suggested that NRM reduced edema, mucosal damage, and the loss of crypts induced by HFD and DSS. In addition, NRM decreased the serum levels of pro-inflammatory cytokines, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 and inhibited the mRNA expressions of these cytokines, and iNOS and COX-2 in colon mucosa (P < 0.05). CONCLUSION: The results suggest that NRM has an anti-inflammatory effect against HFD and DSS-induced colitis in mice, and that these effects are due to the amelioration of HFD and/or DSS-induced inflammatory reactions.

• Journal of Nutrition and Health
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• 제51권1호
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• pp.14-22
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• 2018

본 연구는 LUT이 고지방식이로 비만이 유도된 C57BL/6 마우스의 대장암 발생에 미치는 영향을 분석하기 위해 실험동물을 각 10마리씩 정상식이 (ND)군, 고지방식이 (HFD)군, HFD + 0.0025% LUT 보충 (HFD LL)군, 그리고 HFD + 0.005% LUT 보충 (HFD HL)군의 4군으로 분류하였다. 각 실험군은 AOM을 1회 복강 주사하고 AOM 투여 1주일 후 총 3 cycle의 1 ~ 2% 농도의 DSS를 음용수로 공급하여 대장암을 유발하였다. 실험식이는 AOM 발암시점부터 총 11주간 급여하였다. 연구결과, 군간 식이섭취량의 차이는 없었으나 HFD 급여군에서 체중과 식이효율의 유의적인 증가가 나타났으며 HFD군과 비교했을 때 LUT 보충에 따른 체중의 변화는 없었다. 그러나 LUT 보충은 ND군에 비해 HFD군에서 나타난 대장 무게/길이 비, 대장종양 수, 혈장 $TNF-{\alpha}$ 농도, 대장 iNOS와 COX-2 발현을 유의적으로 감소시켰으며 그 효과는 HFD HL군이 HFD LL군보다 높았다. 이러한 결과는 체중조절과는 별개로 LUT이 고지방식이에 의한 대장의 염증반응 억제를 통하여 비만과 연관된 대장암 발생을 억제할 수 있음을 제시하며 향후 비만에 의한 인슐린 저항성 및 adipokine 분비, 그리고 장내 균총 변화에 따른 대장 점막세포 증식과 대장암 발생에 LUT이 어떤 영향을 미치는지에 대한 연구를 더 깊이 있게 수행한다면 비만으로 인한 대장암 발생에 LUT이 효과적인 화학적 예방 (chemoprevention)제로 활용될 수 있을 것으로 기대한다.

• Molecules and Cells
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• 제38권12호
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• pp.1037-1043
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• 2015

The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. 1 TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-$phosphoelF2{\alpha}$-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance.

• 대한한방소아과학회지
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• 제33권2호
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• pp.22-31
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• 2019

Objective This study is to learn the effects of Hataedock method using Coptidis rhizoma and Glycyrrhiza uralensis mixed extract on inflammatory response in allergic rhinitis-induced obese NC/Nga mice. Materials and Methods The mice were fed with high fat-diet to be obese, and were divided into 3 groups as follows; allergic rhinitis-induced obese mice group with Hataedock method (CGT, n=10), no treatment group (Ctrl), allergic rhinitis elicited obese mice group (ARE). To induce allergic rhinitis, NC/Nga mice of 3 weeks age were sensitized on 7, 8 and 9 weeks by ovalbumin antigen in intraperitoneal space. After 7 days of final sensitization, allergic rhinitis was initially induced in mice through nasal cavities for 5 days. After 1-week, allergic rhinitis was induced again by the same method. Histological examination was used to identify distribution of IL-4, CD40, STAT6, $Fc{\varepsilon}RI$, substance P, MMP-9, NF-${\kappa}B$ p65, iNOS and COX-2. Results Hataedock method significantly reduced IL-4, STAT6 and CD40 response (p<0.05). In CGT, the inhibition of Th2 differentiation decreased inflammatory mediators such as $Fc{\varepsilon}RI$, substance P, MMP-9, NF-${\kappa}B$ p65, iNOS and COX-2 (all p<0.05). The immunological improvement led reduction of respiratory epithelial damage and mucin secretion in goblet cell. Conclusion The results of this study show that the Hataedock method suppresses the expression of allergic rhinitis by decreasing the inflammatory mediators through the regulation of Th2 differentiation even when the inflammation reaction is increased by obesity. Therefore, Hataedock may have potential preventive measure of allergic rhinitis accompanied by obese.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.335-344
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• 2019

Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.

• 대한임상검사과학회지
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• 제54권1호
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• pp.9-14
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• 2022

궤양성 대장염은 면역학적인 이상과 유전적인 요소에 의해 대장의 점막 또는 점막밑층에 염증을 유발하는 질환이다. 이전 연구에 의하면, 비만은 궤양성 대장염의 유병률을 높이고, 진행을 악화시키는 것으로 보고되었다. 따라서 본 연구에서는 커큐민이 비만에 의한 대장염의 진행을 억제하는지에 대해 조사하였다. 비만을 유도하기 위해 고지방 식이로 마우스를 사육하였고, 커큐민의 염증억제 효과를 확인하기 위해 고지방 식이와 함께 커큐민을 섭취시켰다. 궤양성 대장염을 유도하기 위해서 DSS를 경구투여 하고 대장염의 임상 증상을 관찰하였다. 대장염의 진행을 확인하기 위해 질병활성지수와 결장의 길이를 측정하였다. 커큐민에 의한 대장염 완화를 조직학적으로 평가하기 위해 결장, 간, 복부지방의 조직표본을 제작하고 H&E 및 Alcian blue-PAS 염색법으로 분석하였다. 커큐민은 질병활성지수의 점수를 감소시키고, 결장의 길이가 짧아지는 것을 억제하는 것으로 확인하였다. 또한, 비만으로 악화된 궤양성 대장염의 결장 조직에서 염증세포 침윤과 점막손상을 억제하였다. 커큐민은 간의 지방증과 복부지방의 지방세포를 유의하게 감소시키는 것으로 확인하였다. 결론적으로 커큐민은 비만에 의한 대장염의 진행을 억제함으로써 궤양성 대장염을 치료할 수 있는 치료제로서 활용될 것으로 사료된다.

• Journal of Nutrition and Health
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• 제54권5호
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• pp.448-458
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• 2021

본 연구는 뽕나무 열매 착즙 분말 (MJ)이 지방세포 분화과정에서 염증에 관여하는 유전자 발현 및 miR-132/143 조절에 미치는 효과에 중점을 두고 조사하였다. MJ는 3T3-L1 지방세포 분화 동안 지질축적이 억제되었고 PPAR-γ, CEBP-α 및 aP2와 같은 지방형성 유전자 발현을 억제하였다. 또한 염증 조절 매개체인 TNF-α, IL-6, MCP-1 및 iNOS 유전자 발현이 MJ 처리에 의해 감소되었다. MJ의 지질 축적 억제 효과는 염증과 지방분화에 관여하는 miR-132/143의 발현 감소와 관련이 있음을 확인하였다. 따라서 MJ는 염증을 동반하는 비만 예방 및 치료에 도움이 될 수 있는 식품 소재로서 가능성이 있음을 시사하고 있다. 그러나 MJ의 주요 성분인 안토시아닌의 생체이용율은 1-2% 미만으로 추정되며 예상되는 표적 조직이나 혈류에서 미량 검출되는 것으로 알려져 있다 [33]. 이를 해결하기 위해서는 생체 내 동물실험을 통한 다각적인 분석이 향후 진행되어야 할 것으로 판단된다.