• 동의생리병리학회지
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• 제26권4호
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• pp.455-461
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• 2012

Obesity is associated with numerous diseases such as type 2 diabetes, hypertension and cancer. Inhibition of adipogenesis is a effectite strategy to anti-obesity. In this study, Galla Chinenisis extract (GCE) inhibited adipocyte differentiation in OP9 cells. There was no cytotoxicity when cells were treated with GCE in designated time intervals, unaffected by concentration. In this cell model, increases in fat storage were inhibited by 2 days treatment with various concentration of GCE, visualized by Oil red-O, BODIPY and DAPI staining. To understand the underlying mechanism at the molecular level, the effects of GCE were examined on the expression of the genes involved in adipogenesis by real-time PCR. In the progress of adipocyte differentiation with GCE-treated, the mRNA level of adipogenic genes such as peroxisome-proliferator-activated receptors gamma ($PPAR{\gamma}$), computer-assisted axial tomography/enhancer binding protein-alpha ($C/EBP{\alpha}$) were decreased. Also, GCE treatment inhibited increase of mRNA expression, which is adipogenic factor such as fatty acid synthase (FAS), hormone-sensitve lipase (HSL), lipoprotein lipase (LPL), and adipocyte-specific lipid binding protein (aP2). Therefore, the result of this study suggest that Galla Chinenisis extract can prevent adipocyte differentiation and GCE may have a great potential as a novel anti-adipogenic agent.

• Molecules and Cells
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• 제43권9호
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• pp.763-773
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• 2020

Recently, tumor microenvironment (TME) and its stromal constituents have provided profound insights into understanding alterations in tumor behavior. After each identification regarding the unique roles of TME compartments, non-malignant stromal cells are found to provide a sufficient tumorigenic niche for cancer cells. Of these TME constituents, adipocytes represent a dynamic population mediating endocrine effects to facilitate the crosstalk between cancer cells and distant organs, as well as the interplay with nearby tumor cells. To date, the prevalence of obesity has emphasized the significance of metabolic homeostasis along with adipose tissue (AT) inflammation, cancer incidence, and multiple pathological disorders. In this review, we summarized distinct characteristics of hypertrophic adipocytes and cancer to highlight the importance of an individual's metabolic health during cancer therapy. As AT undergoes inflammatory alterations inducing tissue remodeling, immune cell infiltration, and vascularization, these features directly influence the TME by favoring tumor progression. A comparison between inflammatory AT and progressing cancer could potentially provide crucial insights into delineating the complex communication network between uncontrolled hyperplastic tumors and their microenvironmental components. In turn, the comparison will unravel the underlying properties of dynamic tumor behavior, advocating possible therapeutic targets within TME constituents.

• 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.

• 대한한의학방제학회지
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• 제25권4호
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• pp.457-469
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• 2017

Obesity is one of the most serious health problem because it induced numerous metabolic syndrome and increases the incidence of various disease, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. In 3T3-L1 adipocytes, increases in reactive oxygens species (ROS) occur with lipid accumulation. NADPH oxidase, producing superoxide anion, may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. In this study, we elucidated the effect of Chaenomeles sinensis koehne extract (CSE) against the development of obesity and the inhibition mechanisms in 3T3-L1 preadiocytes. CSE decreased triglyceride content and inhibited the expression of adipogenic transcription factors including peroxisome proliferator-activated receptor $(PPAR){\gamma}$, CCAT/enhancer binding protein $(C/EBP){\alpha}$ and sterol regulatory element-binding protein (SREBP-1). In addition, CSE highly increased antioxidant activity in a dose-dependent manner. CSE remarkably reduced intracellular ROS increase and NAD(P)H oxidase activity, NOX1, NOX4, Rac1 protein expression, and phosphorylation of p47phox and p67phox We also studied the effect of CSE on weight gain induced by high-fat diet. The oral treatment of CSE (500 mg/kg, body weight) in diet-induced obese (DIO) mice showed decrease in triglyceride and adipocyte size. Therefore, these results indicate that the effect of CSE on anti-obese effects, adipocyte differentiation and reducing triglyceride contents as well as adipocyte size in obese mice, may be associated with inhibition of NAD(P)H oxidase-induced ROS production and adipose transcription factors. These results showed the potential to inhibit the obesity by CSE treatment through controlling the activation of NAD(P)H oxidase in vitro and in vivo obese model.

• Nutrition Research and Practice
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• 제5권3호
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• pp.192-197
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• 2011

The dietary intake of whole grains is known to reduce the incidence of chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. To investigate whether there are anti-adipogenic activities in various Korean cereals, we assessed water extracts of nine cereals. The results showed that treatment of 3T3-L1 adipocytes with Sorghum bicolor L. Moench, Setaria italica Beauvois, or Panicum miliaceum L. extract significantly inhibited adipocyte differentiation, as determined by measuring oil red-O staining, triglyceride accumulation, and glycerol 3-phosphate dehydrogenase activity. Among the nine cereals, P. miliaceum L. showed the highest anti-adipogenic activity. The effects of P. miliaceum L. on mRNA expression of peroxisome proliferator-activated receptor-${\gamma}$, sterol regulatory element-binding protein 1, and the CCAAT/enhancer binding protein-${\alpha}$ were evaluated revealing that the extract significantly decreased the expression of these genes in a dose-dependent manner. Moreover, P. miliaceum L. extract changed the ratio of monounsaturated fatty acids to saturated fatty acids in adipocytes, which is related to biological activity and cell characteristics. These results suggest that some cereals efficiently suppress adipogenesis in 3T3-L1 adipocytes. In particular, the effect of P. miliaceum L. on adipocyte differentiation is associated with the downregulation of adipogenic genes and fatty acid accumulation in adipocytes.

• Parasites, Hosts and Diseases
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• 제58권3호
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• pp.217-227
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• 2020

Trichomonas vaginalis causes inflammation of the prostate and has been detected in tissues of prostate cancers (PCa), prostatitis and benign prostatic hyperplasia. Obesity is a risk factor for PCa and causes a chronic subclinical inflammation. This chronic inflammation further exacerbates adipose tissue inflammation as results of migration and activation of macrophages. Macrophages are the most abundant immune cells in the PCa microenvironment. M2 macrophages, known as Tumor-Associated Macrophages, are involved in increasing cancer malignancy. In this study, conditioned medium (TCM) of PCa cells infected with live trichomonads contained chemokines that stimulated migration of the mouse preadipocytes (3T3-L1 cells). Conditioned medium of adipocytes incubated with TCM (ATCM) contained Th2 cytokines (IL-4, IL-13). Macrophage migration was stimulated by ATCM. In macrophages treated with ATCM, expression of M2 markers increased, while M1 markers decreased. Therefore, it is suggested that ATCM induces polarization of M0 to M2 macrophages. In addition, conditioned medium from the macrophages incubated with ATCM stimulates the proliferation and invasiveness of PCa. Our findings suggest that interaction between inflamed PCa treated with T. vaginalis and adipocytes causes M2 macrophage polarization, so contributing to the progression of PCa.

• 생명과학회지
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• 제24권2호
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• pp.137-147
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• 2014

유근피(Cortex ulmi pumilae)는 항산화, 항염증, 항균, 항암 등 다양한 생리활성이 보고되어 있으며, 뛰어난 소염효과로 예로부터 약재로 사용되어 왔다. 본 연구에서는 3T3-L1 지방전구세포를 이용하여 유근피 추출물의 지방세포 분화에 미치는 영향과 그 기전을 검토하였다. 유근피 추출물을 분화유도제와 동시에 처리한 결과, 3T3-L1 지방전구세포의 세포질 내 triglyceride 생성을 농도의존적으로 감소시켰으며, 지방세포분화 관련 전사인자인 $C/EBP{\alpha}$, $C/EBP{\beta}$ 및 $PPAR{\gamma}$의 발현을 유의적으로 저하시켰다. 다음으로 유근피 추출물을 지방세포 분화 유도 단계별로 처리한 결과, 분화유도제와 동시에 처리한 경우 즉 분화 초기에 처리한 경우가 가장 효과적인 지방세포 분화 억제효능을 보였으며, 이 때 분화초기에 발현되는 $C/EBP{\beta}$의 발현량은 현저하게 감소되었다. 또한 유근피 추출물에 의해 mitotic clonal expansion 단계의 세포증식이 농도의존적으로 억제되는 것을 확인하였으며, 세포주기분석을 통해 G1 arrest를 유발함으로써 증식이 억제 된다는 것을 확인하였다. 또한, G1 arrest는 G1/S 전이 관련 단백질인 p21의 발현 증가, cyclin E의 발현 감소 및 Rb의 인산화 감소에 의한 것임을 확인하였다. 이러한 연구결과들로부터 유근피 추출물은 지방세포 분화 초기 단계에 작용하여 지방세포 분화 관련 전사인자의 발현을 억제하고 mitotic clonal expansion을 저해하여, 지방전구세포의 지방세포로의 분화를 억제하는 항비만 효능을 가지는 천연소재임을 확인하였으며, 따라서 본 연구는 향후 이를 활용한 지속적인 연구를 위한 기초자료로 그 가치가 매우 높을 것이라 생각된다.

• 생명과학회지
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• 제24권5호
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• pp.573-587
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• 2014

혈관신생은 모든 조직의 성장과 발달, 그리고 상처회복 등에 매우 중요하다. 지방조직은 우리 몸에서 가장 혈관이 발달된 조직으로서 각 지방세포들은 모세혈관에 둘러싸여 있으며 신생혈관들은 지방세포에 영양분과 산소를 공급한다. 혈관의 내피세포들은 파라크린 신호경로, 세포외 성분, 세포들 간의 직접적인 작용을 통해 지방세포와 교류한다. 활성화된 지방세포들은 VEGF, FGF-2, leptin, HGF와 같은 혈관신생인자들을 생성하며, 이들은 단독으로 혹은 협력하여 혈관신생을 증가시키고 지방조직의 성장과 대사를 촉진한다. 따라서 혈관신생 억제제들은 비만과 비만관련 질환을 치료하는데 유용할 것으로 생각된다.

• Journal of Gastric Cancer
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• 제8권4호
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• pp.176-181
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• 2008

목적: 지방세포에서 분비되는 렙틴은 식이 조절과 에너지 소비를 통해 체질량의 항상성을 유지할 뿐만 아니라 세포증식을 조절하여 종양의 진행에서도 중요한 역할을 한다. 위암에서 렙틴과 그 수용체가 높게 발현된다고 보고되고 있으나 조직내 발현과 혈장내 렙틴 레벨과의 상관관계에 대해서는 많이 알려져 있지 않다. 본 연구에서는 위암 환자에서 혈청 렙틴 레벨을 측정하고 조직내 렙틴과 렙틴수용체의 발현과의 상관 관계를 알아보고자 하였다. 대상 및 방법: 본원에서 2005년 10월부터 2007년3월까지 위암으로 근치적 위절제술을 시행 받은 사람 중에서 파라핀 포매 보관상태가 양호한 72명을 대상으로 하였다. 면역측정법을 이용하여 혈청 렙틴 레벨을 측정하였고 위암 조직내 렙틴과 렙틴 수용체의 발현상태는 면역조직화학 염색을 시행하여 확인하였으며 임상병리학적 특성과의 연관성을 분석하였다. 결과: 체질량지수가 높은 환자의 혈청내 렙틴 레벨이 높았으며(P=0.01), 렙틴의 혈청 레벨은 Helicobacter pylon (H. pylori) 감염군에서 감소하였다(P=0.008). 위벽 침윤도와 병기가 증가할수록 렙틴 발현율이 높았으며(P=0.014), 렙틴 수용체의 발현은 장형 71.4%, 미만형 28.6%로 장형인 경우에 높았다(P=0.033) 결론: 위암에서 혈청 렙틴과 조직내 렙틴 발현은 상관관계가 없었고 렙틴의 조직내 발현은 병기와 연관이 있었으나 그 작용 기전을 규명하기 위해서는 앞으로 후속적인 연구가 필요할 것으로 생각된다.

• Journal of Ginseng Research
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• 제11권2호
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• pp.145-252
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• 1987

Isolated rat adipocytes are well known to possess opposite pathways of lipid metabolism: lipolysis and ipogenesis. Both of the metabolism respond to various biologically active substances such as epinephrine, ACTH and insulin. Epinephrine and ACTH stimulate lipolysis and insulin accelerates lipogenesis. Recently, Korean red ginseng powder was found to contain adenosine and an acidic poptide which inhibited epinephrine-induced lipolysis and sl imulated insulin-mediated lipogenesis from added glucose. The acidic peptide is consisted mainly of glutamic acid and glucose. Ginsenosides Rb1 and Re inhibited ACTH-induced lipolysis in isolated rat adipocytes, while they did not affect insulinstimulated lipogenesis, Thus, all these substances extracted from Korean red ginseng exhibited selective modulations toward the opposite metabolic pathways in rat adipocyte; They inhibited the lipolysis but not the lipogenesis. We call these substances"selective modulators". Recently, we isolated a toxic substance named "toxohormone-L " from ascites fluid of patients with various malignant tumors. The toxohormone-L stimulated lipolysis in rat adipocytes and induced anorexia in rats. Both the lipolytic and the anorexigenic actions of toxohormone-L were found to be inhibited by ginsenoside Rb2 in Korean red ginseng. Based on these results, physiological signifi¬cances of these substances in Korean red ginseng were discussed. Pan ax ginseng is a medicinal plant long used in treatment of various pathological states including general complaints such as head ache, shoulder ache, chilly constitution and anorexia in cancer patients, There have been many pharmacological studies on Panax ginseng roots. Petkovllreported that oral administration of an aqueous alcoholic extract of ginseng roots decreased the blood sugar levtl of rabbits. Saito2lreported that Panax ginseng suppressed hyperglycemia induced by epinephrine and high carbohydrate diets. These findings suggest that Panax ginseng roots contain insulin-like substances. Previously, we demonstrated that gin¬seng roots contain an insulin-like peptide which inhibits epinephrine-induced lipolysis and stimulated insulin-mediated lipogenesis. In 1984, we suggested that such an insulin-like substance should be called a selective modulator4). Present investigation describes the details of the selective modulators in ginseng roots. During progressive weight loss in patients with various neoplastic disease, depletion of fat stores have been observed. The depletion of body fat during growth of neoplasms is associated with increase in plasma free fatty acids. Recently, we found that the ascites fluid from patients with hepatoma or ovarian tumor and the pleural fluid from patients with malignant lymphoma elicited fatty acid release in slices of rat adipose tissue in vitro. The lipolytic factor, named"toxohormone-L". was purifed from the ascites fluid of patients with hepatoma. The isolated preparation gave a single band on both disc gel electrophoresis and sodium dodecyl sulfate(SDS)-acrylamide gel electrophoresis in the presence of ${\beta}$-mercaptoethanol. Its molecular weight was determined to be 70,000-75,000 and 65,000 by SDS-acrylamide gel electrophoresis and analytical ultracentrifugation, respectively. Injection of toxohormone-L into the lateral ventricle of rats significantly suppressed food and water intakes. There was at least 5 hr delay between its injection and appearance of its suppressive effect. In the present study, we also tried to find a inhibitory substance toward toxohormone-L from root powder of ginseng.