• Nutrition Research and Practice
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• 제18권4호
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• pp.479-497
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• 2024

BACKGROUND/OBJECTIVES: Activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can protect against obesity and obesity-related metabolic conditions. Cryptotanshinone (CT) regulates lipid metabolism and significantly ameliorates insulin resistance. Adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), a receptor for cellular energy metabolism, is believed to regulate brown fat activity in humans. MATERIALS/METHODS: The in vivo study included high-fat-fed obese mice administered orally 200/400 mg/kg/d CT. They were evaluated through weight measurement, the intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test (IPITT), cold stimulation test, serum lipid (total cholesterol, triglycerides, and low-density lipoprotein) measurement, hematoxylin and eosin staining, and immunohistochemistry. Furthermore, the in vitro study investigated primary adipose mesenchymal stem cells (MSCs) with incubation of CT and AMPK agonists (acadesine)/inhibitor (Compound C). Cells were evaluated using Oil Red O staining, Alizarin red staining, flow cytometry, and immunofluorescence staining to identify and observe the osteogenic versus adipogenic differentiation. Quantitative real-time polymerase chain reaction and the Western blot were used to observe related gene expression. RESULTS: In the diet-induced obesity mouse model mice CT suppressed body weight, food intake, glucose levels in the IPGTT and IPTT, serum lipids, the volume of adipose tissue, and increased thermogenesis, uncoupling protein 1, and the AMPK pathway expression. In the in vitro study, CT prevented the formation of lipid droplets from MSCs while activating brown genes and the AMPK pathway. AMPK activator enhanced CT's effects, while the AMPK inhibitor reversed the effects of CT. CONCLUSION: CT promotes adipose tissue browning to increase body thermogenesis and reduce obesity by activating the AMPK pathway. This study provides an experimental foundation for the use of CT in obesity treatment.

• Nutrition Research and Practice
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• 제10권6호
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• pp.623-628
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• 2016

BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype. MATERIALS/METHODS: Male C57BL/6 mice were fed a regular diet (RD), high-fat diet (HFD), or HFD supplemented with quercetin (HF+Que, 0.5g/kg diet) for nine weeks. Inflammatory cytokines and macrophage markers were measured by ELISA and RT-PCR, respectively. HO-1 protein was measured by Western blotting. RESULTS: Quercetin supplementation decreased levels of inflammatory cytokines ($TNF{\alpha}$, IL-6) and increased that of the anti-inflammatory cytokine (IL-10) in the livers of HFD-fed mice. This was accompanied by upregulation of M2 macrophage marker genes (Arg-1, Mrc1) and downregulation of M1 macrophage marker genes ($TNF{\alpha}$, NOS2). In co-cultures of lipid-laden hepatocytes and macrophages, treatment with quercetin induced HO-1 in the macrophages, markedly suppressed expression of M1 macrophage marker genes, and reduced release of MCP-1. Moreover, these effects of quercetin were blunted by an HO-1 inhibitor and deficiency of nuclear factor E2-related factor 2 (Nrf2) in macrophages. CONCLUSIONS: Quercetin reduces obesity-induced hepatic inflammation by promoting macrophage phenotype switching. The beneficial effect of quercetin is associated with Nrf2-mediated HO-1 induction. Quercetin may be a useful dietary factor for protecting against obesity-induced steatohepatitis.

• 한방비만학회지
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• 제20권2호
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• pp.78-87
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• 2020

Objectives: To expand and provide information on the efficacy of herbal medicines, anti-obesity effects were evaluated. In many studies, plant-derived components with anti-obesity efficacies have been investigated for their potential inhibitory effects on 3T3-L1 preadipocyte cells. The purpose of this study was to investigate the anti-obesity effects of 65 herbal medicine in 3T3-L1 preadipocyte cells. Methods: Preferentially, 3T3-L1 cells were treated with 65 herbal medicines (500 ㎍/mL) during differentiation for 8 days. Next, 3T3-L1 cells were treated with selected herbal medicines at concentrations ranging from 50 to 200 ㎍/mL during differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining. The expressions of genes related to adipogenesis were measured by reverse transcription polymerase chain reaction and Western blot analyses. Results: Among the 65 kinds of herbal medicines, 13 herbal medicines that been shown to be effective against the accumulation of lipid droplets were selected. Finally, selected Banhasasim-tang and Samhwangsasim-tang showed inhibitory activity on adipocyte differentiation at 3T3-L1 preadipocytes without affecting cell toxicity. In addition, Banhasasim-tang and Samhwangsasim-tang significantly reduced the expression levels of several adipocyte marker genes including peroxisome proliferator activated receptor-γ and CCAAT/enhancer binding protein-α. Conclusions : These results suggest that the ability of Banhasasim-tang and Samhwangsasimtang has inhibited overall adipogenesis and lipid accumulation in the 3T3-L1 cells. Banhasasim-tang and Samhwangsasim-tang may be a promising medicine for the treatment of obesity and related metabolic disorders.

• 한국가금학회지
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• 제42권1호
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• pp.51-59
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• 2015

본 연구는 밀사에 의한 환경스트레스가 닭의 품종에 따라 스트레스 및 대사 연관 유전자들의 발현에 어떤 영향을 미치는지 알아보고자 실시하였다. 공시계는 한국재래닭과 백색레그혼으로 두 품종 모두 40주령 때 대조구($540cm^2$/수) 및 고밀도구($311cm^2$/수)로 분리하고, 50주령까지 10주간 사육하였다. 사양시험 종료 후, 각 개체의 간으로부터 total RNA를 추출하고, 스트레스, 소포체(ER) 스트레스 및 대사 연관유전자들의 발현을 real-time PCR을 이용하여 분석하였다. 한국재래계는 분석된 모든 스트레스 표지 유전자들의 발현이 밀사구와 대조구 사이에 유의적인 변화를 보이지 않았다. 그러나 백색레그혼의 경우, HSP70과 $HSP90{\alpha}$ 유전자의 발현이 유의적으로 높게 나타났다(P<0.05). 분석된 ATF6, GRP78, SREBP2 등의 발현은 품종 간 차이를 볼 수 없었지만, XBP1의 경우 백색레그혼이 한국재래계에 비하여 높은 발현을 보였다(P<0.05). 분석된 유전자들 중 FABP4, FATP1, ACSL1 등의 경우, 한국재래계에 비하여 백색레그혼에서 높은 유전자 발현을 보였다(P<0.05). GLUT의 발현은 품종 간에는 영향을 받지 않지만, 밀사에 의한 영향을 받고 있음을 보여주었다. 고밀도사양 체계는 닭의 품종과 관계없이 스트레스 요인이 될 수 있으며, 닭의 품종이나 개량의 정도에 따라 스트레스 반응에 대한 유전적 차이가 있음을 시사하고, 또한 밀사와 같은 환경적 스트레스는 간의 지방 및 포도당 대사에 영향을 미칠 수 있음을 보여주었다.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.397-404
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• 2020

Adiponectin secretion-promoting compounds have therapeutic potentials in human metabolic diseases. Diallyl biphenyl-type neolignan compounds, magnolol, honokiol, and 4-O-methylhonokiol, from a Magnolia officinalis extract were screened as adiponectin-secretion promoting compounds in the adipogenic differentiation model of human bone marrow mesenchymal stem cells (hBM-MSCs). In a target identification study, magnolol, honokiol, and 4-O-methylhonokiol were elucidated as PPARα and PPARγ dual modulators. Diallyl biphenyl-type neolignans affected the transcription of lipid metabolism-associated genes in a different way compared to those of specific PPAR ligands. The diallyl biphenyl-type neolignan structure provides a novel pharmacophore of PPARα/γ dual modulators, which may have unique therapeutic potentials in diverse metabolic diseases.

• Journal of Microbiology and Biotechnology
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• 제31권11호
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• pp.1568-1575
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• 2021

Obesity and related metabolic diseases are major problems worldwide. Some probiotics are currently considered potential therapeutic strategies for obesity. We aimed to investigate the anti-obesity efficacy of Latilactobacillus sakei WIKIM31 in obese mice induced by a high fat diet. The administration of a high-fat diet with L. sakei WIKIM31 reduced body weight gain, epididymal fat mass, triglyceride and total cholesterol levels in the blood, and remarkably decreased the expression of lipogenesis-related genes in the epididymal adipose tissue and liver. Interestingly, intake of L. sakei WIKIM31 improved gut barrier function by increasing the gene expression of tight junction proteins and suppressing the inflammatory responses. Additionally, L. sakei WIKIM31 enhanced the production of short-chain fatty acids, such as butyrate and propionate, in the intestinal tract. These results showed that L. sakei WIKIM31 can be used as a potential therapeutic probiotic for obesity.

• BMB Reports
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• 제49권2호
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• pp.105-110
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• 2016

Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli.

• Nutrition Research and Practice
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• 제15권4호
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• pp.431-443
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• 2021

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on high-cholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidation-related gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCD-fed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS: The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

• Journal of Ginseng Research
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• 제46권3호
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• pp.357-366
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• 2022

Background: Withania somnifera (Solanaceae), generally known as Indian ginseng, is a medicinal plant that is used in Ayurvedic practice for promoting health and longevity. This study aims to identify the bioactive metabolites from Indian ginseng and elucidate their structures. Methods: Withanolides were purified by chromatographic techniques, including HPLC coupled with LC/MS. Chemical structures of isolated withanolides were clarified by analyzing the spectroscopic data from 1D and 2D NMR, and HR-ESIMS experiment. Absolute configurations of the withanolides were established by the application of NMR chemical shifts and ECD calculations. Anti-adipogenic activities of isolates were evaluated using 3T3-L1 preadipocytes with Oil Red O staining and quantitative real-time PCR (qPCR). Results: Phytochemical examination of the roots of Indian ginseng afforded to the isolation of six withanolides (1-6), including three novel withanolides, withasilolides GeI (1-3). All the six compounds inhibited adipogenesis and suppressed the enlargement of lipid droplets, compared to those of the control. Additionally, the mRNA expression levels of Fabp4 and Adipsin, the adipocyte markers decreased noticeably following treatment with 25 µM of 1-6. The active compounds (1-6) also promoted lipid metabolism by upregulating the expression of the lipolytic genes HSL and ATGL and downregulating the expression of the lipogenic gene SREBP1. Conclusion: The results of our experimental studies suggest that the withasilolides identified herein have anti-adipogenic potential and can be considered for the development of therapeutic strategies against adipogenesis in obesity. Our study also provides a mechanistic rationale for using Indian ginseng as a potential therapeutic agent against obesity and related metabolic diseases.

• 생명과학회지
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• 제29권10호
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• pp.1144-1151
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• 2019

비알코올성 지방간은 만성 간 질환으로 비만, 고혈압, 비만, 이상지질혈증과 같은 다양한 대사증후군과 연관되어 있다. 꾸지뽕은 한국을 포함한 동아시아 국가에서 다양한 질병에 사용되는 약용작물로 본 연구에서는 유리지방산에 의해 지방축적이 유도된 세포 내에서 꾸지뽕 열매 추출물의 비알코올성 지방간 개선 효과와 기전을 규명하였다. 꾸지뽕 열매 추출물은 지방 축적 및 중성지방, 콜레스테롤 생성 및 HMG 환원효소의 활성을 억제하였다. 또한 지방생성과 관련된 유전자인 SREBP-1, FAS, SCD-1, SREBP-2의 발현을 억제 하였으며 AMPK의 활성화를 억제하였다. 본 연구결과를 통해서 꾸지뽕 열매 추출물이 유리지방산에 의해 유도된 지방 축적을 억제하고 AMPK/SREBP 신호전달 경로를 조절하여 억제 활성을 나타냄을 밝히며, 비알코올성 지방간의 예방 및 개선을 위한 천연물 소재로 활용될 수 있을 것으로 사료된다.