• BMB Reports
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• 제45권3호
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• pp.141-146
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• 2012

Protein tyrosine phosphatase 1B (PTP1B) is important in the regulation of metabolic diseases and has emerged as a promising signaling target. Previously, we reported the PTP1B inhibitory activity of Rheum undulatum (RU). In the present study, we investigated the metabolic regulatory effects of RU in a high-fat diet (HFD) model. RU treatment significantly blocked body weight gain, which was accompanied by a reduction of feed efficiency. In addition, it led to a reduction of liver weight mediated by overexpression of PPAR${\alpha}$ and CPT1 in the liver, and an increase in the expression of adiponectin, aP2, and UCP3 in adipose tissue responsible for the reduction of total and LDL-cholesterol levels. Chrysophanol and physcion from RU significantly inhibited PTP1B activity and strongly enhanced insulin sensitivity. Altogether, our findings strongly suggest that 2 compounds are novel PTP1B inhibitors and might be considered as anti-obesity agents that are effective for suppressing body weight gain and improving lipid homeostasis.

• Clinical and Experimental Pediatrics
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• 제63권3호
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• pp.110-114
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• 2020

Background: Subclinical hypothyroidism (SH) is a common condition in obese children. However, its effect on glucose and lipid metabolism in obese children remains controversial. Purpose: The present study aimed to investigate the association between SH and metabolic parameters. Methods: A total of 215 obese children and adolescents aged 6-18 years were included in this retrospective cross-sectional study. The patients' anthropometric measurements such as thyrotropin (TSH), free thyroxine (fT4), fasting plasma glucose, and insulin levels, as well as homeostasis model assessment for insulin resistance (HOMA-IR) index, and lipid profiles were evaluated. The patients were allocated to the SH group (fT4 normal, TSH 5-10 mIU/L) (n=77) or the control group (fT4 normal, TSH<5 mIU/L) (n=138). The glucose and lipid metabolisms of the 2 groups were compared. Results: SH was identified in 77 of 215 patients (36%). Mean body mass index was similar in both groups. The mean serum insulin, HOMA-IR, and triglyceride (TG) levels were higher and the mean high-density lipoprotein cholesterol level was lower in the SH group than in the control group (P=0.007, P=0.004, P=0.01, and P=0.02, respectively). A positive correlation was observed between TSH level and insulin level, HOMA-IR, and TG level. Conclusion: SH was identified in some of the obese children and adolescents. A clear association was observed between SH, insulin resistance, and dyslipidemia in obese children.

• Molecules and Cells
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• 제43권5호
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• pp.431-437
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• 2020

The hypothalamus is a crucial organ for the maintenance of appropriate body fat storage. Neurons in the hypothalamic arcuate nucleus (ARH) detect energy shortage or surplus via the circulating concentrations of metabolic hormones and nutrients, and then coordinate energy intake and expenditure to maintain energy homeostasis. Malfunction or loss of hypothalamic ARH neurons results in obesity. Accumulated evidence suggests that hypothalamic inflammation is a key pathological mechanism that links chronic overconsumption of a high-fat diet (HFD) with the development of obesity and related metabolic complications. Interestingly, overnutrition-induced hypothalamic inflammation occurs specifically in the ARH, where microglia initiate an inflammatory response by releasing proinflammatory cytokines and chemokines in response to excessive fatty acid flux. Upon more prolonged HFD consumption, astrocytes and perivascular macrophages become involved and sustain hypothalamic inflammation. ARH neurons are victims of hypothalamic inflammation, but they may actively participate in hypothalamic inflammation by sending quiescence or stress signals to surrounding glia. In this mini-review, we describe the current state of knowledge regarding the contributions of neurons and glia, and their interactions, to HFD-induced hypothalamic inflammation.

• Biomolecules & Therapeutics
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• 제24권6호
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• pp.589-594
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• 2016

Insulin is a peptide hormone of the endocrine pancreas and exerts a wide variety of physiological actions in insulin sensitive tissues, such as regulation of glucose homeostasis, cell growth, differentiation, learning and memory. However, the role of insulin in osteoblast cells remains to be fully characterized. In this study, we demonstrated that the insulin (100 nM) has the ability to stimulate the phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK) and the levels of inhibin-${\beta}E$ in the osteoblast-like UMR-106 cells. This insulin-stimulated activities were abolished by the PI3K and MEK1 inhibitors LY294002 and PD98059, respectively. This is the first report proving that insulin is a potential candidate that enables the actions of inhibin-${\beta}E$ subunit of the TGF-${\beta}$ family. The current investigation provides a foundation for the realization of insulin as a potential stimulator in survival signaling pathways in osteoblast-like UMR-106 cells.

• Laboraroty Animal Research
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• 제34권4호
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• pp.140-146
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• 2018

Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.

• BMB Reports
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• 제56권4호
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• pp.246-251
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• 2023

Obesity increases the risk of mortality and morbidity because it results in hypertension, heart disease, and type 2 diabetes. Therefore, there is an urgent need for pharmacotherapeutic drugs to treat obesity. We performed a screening assay using natural products with anti-adipogenic properties in 3T3-L1 cells and determined that tschimganidine, a terpenoid from the Umbelliferae family, inhibited adipogenesis. To evaluate the anti-obesity effects of tschimganidine in vivo. Mice were fed either a normal chow diet (NFD) or a high-fat chow diet (HFD) with or without tschimganidine for 12 weeks. Treatment with tschimganidine decreased lipid accumulation and adipogenesis, accompanied by reduced expression of adipogenesis and lipid accumulation-related factors. Tschimganidine significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased that of AKT. Depletion of AMPK relieved the reduction in lipid accumulation resulting from tschimganidine treatment. Moreover, tschimganidine administration drastically reduced the weight and size of both gonadal white adipose tissue (WAT) and blood glucose levels in high-fat diet-induced obese mice. We suggest that tschimganidine is a potent anti-obesity agent, which impedes adipogenesis and improves glucose homeostasis. Tschimganidine can then be evaluated for clinical application as a therapeutic agent.

• Journal of Animal Science and Technology
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• 제66권2호
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• pp.425-437
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• 2024

Exercise plays an important role in regulating energy homeostasis, which affects the diversity of the intestinal microbial community in humans and animals. To the best of the authors' knowledge, few studies have reported the associations between horse gut microbiota along with their predicted metabolic activities and the athletic ability of Jeju horses and Thoroughbreds living in Korea. This study was conducted to investigate the association between the gut microbiota and athletic performance in horses. This study sequenced the V3 and V4 hypervariable regions of the partial 16S rRNA genes obtained from racehorse fecal samples and compared the fecal microbiota between high- and low-performance Jeju horses and Thoroughbreds. Forty-nine fecal samples were divided into four groups: high-performance Jeju horses (HJ, n = 13), low-performance Jeju horses (LJ, n = 17), high-performance Thoroughbreds (HT, n = 9), and low-performance Thoroughbreds (LT, n = 10). The high-performance horse groups had a higher diversity of the bacterial community than the low-performance horse groups. Two common functional metabolic activities of the hindgut microbiota (i.e., tryptophan and succinate syntheses) were observed between the low-performance horse groups, indicating dysbiosis of gut microbiota and fatigue from exercise. On the other hand, high-performance horse groups showed enriched production of polyamines, butyrate, and vitamin K. The racing performance may be associated with the composition of the intestinal microbiota of Jeju horses and Thoroughbreds in Korea.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제7권2호
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• pp.228-238
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• 2004

목적: 소아 비만클리닉에서 시행하는 선별검사로 대사증후군의 위험인자를 미리 인지하여 비만아가 치료를 지속적으로 할 수 있도록 지도하는데 도움을 주고자 하였다. 대상: 2000년 2월부터 2004년 6월까지 이대 목동병원 소아 비만클리닉을 방문한 비만아에서 의무기록이 충실하고 체질량지수(BMI)가 95 백분위수 이상인 88명(남 52명, 여 36명)을 대상으로 하였다. 방법: 비만아에서 BMI를 계산하고 혈압은 안정 상태에서 두 번 측정하여 평균을 구하였다. 12시간 공복 후에 혈청 지질(중성지방, 총콜레스테롤, 고밀도 콜레스테롤, 저밀도 콜레스테롤), 혈당과 혈중 인슐린 농도를 측정하였다. 인슐린 저항성 지표로 fasting insulin to glucose ratio (FIGR), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI)를 이용하였다. 결 과: 비만아 88명 중 53명(60.2%)에서 하나 이상의 대사증후군의 위험 인자를 보였다. 고혈압은 13명(14.8%), 중성지방 ${\geq}150mg/dL$ 13명(14.8%), 총콜레스테롤 ${\geq}200mg/dL$ 23명(26.1%), 고밀도 콜레스테롤 ${\leq}40mg/dL$ 13명(14.8%), 저밀도 콜레스테롤 ${\geq}130mg/dL$ 11명(12.5%)이었으며 고인슐린 혈증은 11명(12.5%)이었다. BMI는 수축기 혈압(r=0.535), 고밀도 콜레스테롤(r=-0.214), 인슐린 농도(r=0.342), HOMA-IR (r=0.346), FIGR (r=0.329), QUICKI (r=-0.22)와 유의한 상관 관계를 보였다. 인슐린 농도(r=0.233), HOMA-IR (r=0.234)은 수축기 혈압과, FIGR은 수축기 혈압(r=0.227) 및 저밀도 콜레스테롤(r=0.223)과, QUICKI는 혈당(r=-0.308)과 각각 유의한 상관관계를 보였다. 선별검사에서 대사증후군의 위험 인자가 많을수록 인슐린 저항성(HOMA-IR, FIGR)이 유의하게 증가하였다. 한편 인슐린 저항성을 가장 잘 설명하는 인자로는 BMI, 중성지방, 총콜레스테롤이었다. 결론: 소아 비만클리닉을 방문하는 비만아에서 이미 대사증후군이 시작되고 있으므로 행동 수정, 식사조절 및 운동 처방뿐 아니라 혈압, 지질, 혈당, 인슐린 농도 등을 정기적으로 검사하여 적극적으로 관리해야 한다.

• 대한임상검사과학회지
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• 제47권4호
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• pp.324-331
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• 2015

갑상샘 호르몬은 교감신경계와의 상호작용으로 세포의 에너지 대사조절 및 항상성 유지에 중요한 역할을 한다. 본 연구는 건강검진을 실시한 성인 남성을 대상으로 갑상샘 호르몬과 대사증후군 위험요인간의 연관성을 밝히고자 하였다. 경기지역 일개 종합병원에서 2011년 1월부터 2013년 12월까지 건강검진센터에서 종합건강검진을 실시한 20세 이상 80세 이하의 남성 12,250명을 대상으로 하였다. 대사증후군은 American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI, 2005)에서 제시한 진단 기준에 따랐으며, 3개 이상의 위험요인을 가진 경우 대사증후군으로 진단하였다. 정상군보다 대사증후군 진단군에서 FT4가 낮았으며(p<0.001), TSH는 대사증후군 유무에 따른 차이는 없었다. 또한 FT4는 대사증후군 위험요인 중 허리둘레, 중성지방에 영향을 미치는 것으로 나타났으며(각각 p<0.001), FT4의 가장 낮은 사분위수가 가장 높은 사분위수보다 HbA1c, 인슐린, HOMA-IR, hs-CRP 농도가 높았다(각각 p<0.001). FT4는 허리둘레, 중성지방에 영향을 미치는 것으로 나타났으나, TSH는 대사증후군 위험요인에 영향을 미치지 않는 것으로 나타났다. 또한 FT4의 가장 높은 분위수의 대사증후군 발생위험이 가장 낮은 분위수보다 낮게 나타났다.

• Nutrition Research and Practice
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• 제8권2호
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• pp.177-182
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• 2014

BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with energy homeostasis. We investigated whether aged garlic extract (AGE) and exercise training intervention could improve body weight, insulin sensitivity, skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats were fed a ND (normal diet, n=5) or HFD (n=28) for 6 weeks. After 6 weeks, all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n=5), HFD (high-fat diet, n=7), HFDA (high-fat diet + aged garlic extract, n=7), HFDE (high-fat diet + exercise, n=7), and HFDEA (high-fat diet + exercise + aged garlic extract, n=7). Exercise groups performed treadmill exercises for 15-60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for 4 weeks. RESULTS: Significant decreases in body weight were observed in the ND, HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention affected the masses of the gastrocnemius muscle or liver. There were no significant differences in glucose levels across the groups. The homeostatic model assessments of insulin resistance were significantly higher in the HFD group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or exercise in obese rats. AGE supplementation and exercise training did not affect skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin sensitivity in obese rats. CONCLUSION: Our results suggest that the protection against HFD-induced increases in body fat/weight and insulin resistance that are provided by AGE supplementation and exercise training may not be mediated by the regulation of FNDC-5 or irisin.