• Animal cells and systems
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• 제14권4호
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• pp.253-259
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• 2010

Artemisia capillaris Thunb. is widely used in the herbal medicine field. This study describes the antidepressant effect of a flavonoid (chlorogenic acid) isolated from the Artemisia capillaris Thunb. The expression of the pituitary gland and hypothalamic POMC mRNA or plasma ${\beta}$-endorphin levels were increased by extract of Artemisia capillaris Thunb. or its flavoniod administered orally. In addition, antidepressant activity was studied using the tail suspension test (TST), the forced swimming test (FST) and the rotarod test in a chronically restrained immobilization stress group in mice. After restraint stress (2 h/day for 14 days), animals were kept in a cage for 14 days without any further stress, but with drugs. Mice were fed with a diet supplemented for 14 days and during the behavioral test period with chlorogenic acid (30 mg/kg/day). POMC mRNA or the plasma ${\beta}$-endorphin level was increased by the extract of Artemisia capillaris Thunb. and its flavoniod. In addition, the immobility time in TST and FST was significantly reduced by chlorogenic acid. In the rotarod test, the riding time remained similar to that of the control group at 15 rpm. Our results suggest that the flavonoid (chlorogenic acid) isolated from Artemisia capillaris Thunb. shows a potent antidepressant effect.

• Molecules and Cells
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• 제41권3호
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• pp.244-255
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• 2018

Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesity-associated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + ${\alpha}$-bungaratoxin (${\alpha}-BGT$) group (As IV+${\alpha}-BGT$ group). As IV ($20mg{\cdot}Kg^{-1}{\cdot}d^{-1}$) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of ${\alpha}7nAChR$, inhibitor of nuclear factor ${\kappa}B$ kinase subunit ${\beta}/nuclear$ factor ${\kappa}B$ ($IKK{\beta}/NF-KB$) and pro-inflammatory cytokines ($IL-1{\beta}$ and $TNF-{\alpha}$) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of ${\alpha}7nAChR$. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated ${\alpha}7nAchR$ and suppressed $IKK{\beta}/NF-KB$ signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of ${\alpha}7nAChR$ selective antagonist ${\alpha}-BGT$ could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesityassociated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased ${\alpha}7nAchR$ expression.

• 대한소아치과학회지
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• 제29권2호
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• pp.278-284
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• 2002

RAW 264.7과 이것이 분화한 파골세포양 세포에서 파골세포 분화관련유전자의 전체적인 유전자 발현을 조사하기 위해 cDNA array 방법을 사용하였다. 1176 cDNA spot grid가 있는 Mouse Atlas cDNA array 결과를 확인하기 위하여 역전사 효소 중합반응 검사를 시행하였다. cDNA array 결과 6개의 유전자가 2.5% 이상 발현이 증가하였으며(PKC beta II, POMC, PTEN 등), 16개의 유전자가 2.5%이상 발현이 감소하였다(Osteopontin, Cyclin D1, Cathepsin C, PTMA 등). PKC beta II 유전자의 역전사-효소 중합 반응검사결과 이 유전자를 확인할 수 있었다. 파골세포 분화 결과 RAW 264.7세포주에 비해 파골세포양 세포에서 PKC beta II 유전자의 발현이 많았다. 파골세포 분화 관련 유전자는 RAW 264.7 세포주와 이것이 분화된 파골세포양 세포와 차이를 보였고, 이 유전자의 발현증가와 RAW 264.7 세포주의 파골세포 분화와 연관을 보였다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.15-23
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• 2003

Interest in the regulation of body weight and the pathological physiology of obesity has been rekindled by the cloning of the obese(ob) gene and identification of its product, leptin, in 1994. The first publication appeared in Nature and is a milestone of obesity research. The remarkable metabolic effects of leptin in rodents are: a) inhibition of food intake, b) stimulation of energy expenditure, and c) reversal of obesity. These effects, though mostly desirable, have not been fully demonstrated in humans. The central action of leptin in the regulation of body weight includes two pathways in rodents: a) When the body weight increasing, more leptin is secreted from adipose tissue, which acts on hypothalamus, probably through a POMC or MSH pathway via M4 receptor, initiates a series of response to obesity, i.e. sympathetic tone increased, energy expenditure enhanced and food intake reduced. b) When body weight reduced, leptin concentration decreased with the shrinkage of fat mass, which may also act on the hypothalamus, probably through a NPY-Y5 receptor pathway. Then a cascade of response to hungry was induced, i.e. increase of parasympathetic tone and food intake, decrease of energy expenditure and body temperature, as well as shut-down of the reproductive function.

• Journal of Yeungnam Medical Science
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• 제30권1호
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• pp.4-9
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• 2013

Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.

• Asian-Australasian Journal of Animal Sciences
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• 제25권9호
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• pp.1300-1308
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• 2012

The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a key part of a kinase-signaling cascade that acts to maintain energy homeostasis. The objective of this experiment was to investigate the possible effects of fasting and refeeding on the gene expression of hypothalamic AMPK, some appetitive regulating peptides and lipid metabolism related enzymes. Seven-day-old male broiler (Arbor Acres) chicks were allocated into three equal treatments: fed ad libitum (control); fasted for 24 h; fasted for 24 h and then refed for 24 h. Compared with the control, the hypothalamic gene expression of $AMPK{\alpha}2$, $AMPK{\beta}1$, $AMPK{\beta}2$, $AMPK{\gamma}1$, Ste20-related adaptor protein ${\beta}$ ($STRAD{\beta}$), mouse protein $25{\alpha}$ ($MO25{\alpha}$) and agouti-related peptide (AgRP) were increased after fasting for 24 h. No significant difference among treatments was observed in mRNA levels of $AMPK{\alpha}1$, $AMPK{\gamma}2$, LKB1 and neuropeptide Y (NPY). However, the expression of $MO25{\beta}$, pro-opiomelanocortin (POMC), corticotropin-releasing hormone (CRH), ghrelin, fatty acid synthase (FAS), acetyl-CoA carboxylase ${\alpha}$ ($ACC{\alpha}$), carnitine palmitoyltransferase 1 (CPT-1) and sterol regulatory element binding protein-1 (SREBP-1) were significantly decreased. The present results indicated that 24 h fasting altered gene expression of AMPK subunits, appetite regulation peptides and lipometabolism related factors in chick's hypothalamus; the hypothalamic FAS signaling pathway might be involved in the AMPK regulated energy homeostasis and/or appetite regulation in poultry.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 제4회 추계심포지움
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• pp.153-159
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• 1996

${\alpha}$-Melanotropin (Ac-Ser-Tyr- Ser-Met-Glu$\^$5/-His-Phe-Arg-Trp-Gly$\^$10/-Lys-Pro-Val-NH$_2$) is one of the first peptide hormones to be isolated and have its structure determined. It was early recognized to have essentially the same N-terminal tridecapeptide sequence as adrenocorticotropic hormone (ACTH) except that the N-terminal was acetylated in the case of ${\alpha}$-MSH but not in the case of ACTH, indicating that their biosyntheses were different (Figure 1). Subsequently it was discovered that ${\alpha}$-MSH and ACTH were derived from the same gene, currently referred to as proopiomelanocortin (POMC). Its original bioactivity was pigmentation, but it also was recognized that it may have activity in the central nervous system, though the precise nature of these central activities have been controversial. The recent cloning and expression of five melanocortin receptors, with the MC3 and MC4 receptors found primarily in the brain and the MC5 receptor (MC5-R) found throughout the body, has provided new impetus to understand the structure-activity relationships of ${\alpha}$-MSH at these receptors. The effects of ${\alpha}$-MSH on pigmentation are mediated by the MC1-R expressed specifically on the surface of melanocytes. Similarly the MC2-R is involved in the regulation of adrenal steroidogenesis by ACTH. However, given the complexity of expression of the MC3, MC4, and MC5 receptors, it has not been possible to identify any simple correlations between these receptors and the reported biological activities of the melanocortin peptides. Consequently, potent and receptor specific agonists and especially antagonists would be extremely valuable tools for the determination of the physiological roles of the MC3, MC4, and MC5 receptors. Though the extensive structure-activity relationships have provided much information on agonist activity related to pigmentary effects, only recently has it been possible to begin to systematically develop potent and selective antagonists.

• Nutrition Research and Practice
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• 제16권3호
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• pp.285-297
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• 2022

BACKGROUND/OBJECTIVES: Korean pine nut oil (PNO) has been reported to suppress appetite by increasing satiety hormone release. However, previous studies have rendered inconsistent results and there is lack of information on whether dietary Korean PNO affects the expression of satiety hormone receptors and hypothalamic neuropeptides. Therefore, our study sought to evaluate the chronic effects of Korean PNO on the long-term regulation of energy balance. MATERIALS/METHODS: Five-week-old male C57BL/6 mice were fed with control diets containing 10% kcal fat from Korean PNO or soybean oil (SBO) (PC or SC) or high-fat diets (HFDs) containing 35% kcal fat from lard and 10% kcal fat from Korean PNO or SBO (PHFD or SHFD) for 12 weeks. The expression of gastrointestinal satiety hormone receptors, hypothalamic neuropeptides, and genes related to intestinal lipid absorption and adipose lipid metabolism was then measured. RESULTS: There was no difference in the daily food intake between PNO- and SBO-fed mice; however, the PC and PHFD groups accumulated 30% and 18% less fat compared to SC and SHFD, respectively. Korean PNO-fed mice exhibited higher messenger RNA (mRNA) expression of Ghsr (ghrelin receptor) and Agrp (agouti-related peptide) (P < 0.05), which are expressed when energy consumption is low to induce appetite as well as the appetitesuppressing neuropeptides Pomc and Cartpt (P = 0.079 and 0.056, respectively). Korean PNO downregulated jejunal Cd36 and epididymal Lpl mRNA expressions, which could suppress intestinal fatty acid absorption and fat storage in white adipose tissue. Consistent with these findings, Korean PNO-fed mice had higher levels of fecal non-esterified fatty acid excretion. Korean PNO also tended to downregulate jejunal Apoa4 and upregulate epididymal Adrb3 mRNA levels, suggesting that PNO may decrease chylomicron synthesis and induce lipolysis. CONCLUSIONS: In summary, Korean PNO attenuated body fat accumulation, and appeared to prevent HFD-induced dysregulation of the hypothalamic appetite-suppressing pathway.

• 한국발생생물학회지:발생과생식
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• 제13권4호
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• pp.207-215
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• 2009

시상하부-뇌하수체-생식소(hypothalamus-pituitary-gonad, HPG) 호르몬 축의 활성에 영향을 미치는 수많은 인자들은 생식 기능을 조절하고, 사춘기 개시와 폐경기 진입과 같은 뚜렷한 생식 능력의 단계 전이를 초래한다. 지방세포로부터 분비되는 다기능적 호르몬인 leptin의 발견 이후, 곧 이어 생식과 신체의 에너지 균형 사이의 긴밀한 관계에 대한 증거들이 밝혀졌다. 위장관으로부터 분비되는 또 다른 다기능 호르몬인 ghrelin은 이미 알려져 있던 growth hormone secretagogue receptor(GHSR)의 내인성 리간드이며, 에너지 항상성의 조절에서 leptin에 상응하는 물질로 알려졌다. 예상대로, ghrelin 또한 HPG 축의 활성의 조절을 통해 생식 능력을 조절함이 증명되었다. 이 논문은 ghrelin의 발견과 유전자 구조, 조직 내의 분포, 그리고 역할과 HPG 축에서의 생식 호르몬 분비 조절에 대한 포유동물의 생식에서의 ghrelin-GHSR 신호에 관한 최신 정보를 요약한 것이다. 뇌하수체에서의 POMC 유전자 발현과 유사하게, preproghrelin 유전자는 alternative splicing과 번역 후 변형(posttranslational modification)을 거치는 복잡한 레퍼토리의 전사체들과 펩티드 산물을 만들어 낸다. 에너지 항상성을 제외한 신체 생리 기능의 조절에서의 preproghrelin 유전자 산물의 역할에 관한 정보는 제한적이지만, 신진 대사와 생식 사이에서의 ghrelin의 상호작용에 관해서는 충분한 증거들이 있다. 흰쥐와 인간에서, ghrelin 수용체인 GHSRs(GHSR1a와 GHSR1b)의 분포는 본래 ghrelin의 표적으로 여겨진 시상하부와 뇌하수체뿐만 아니라 정소와 난소에서도 확인되었다. 뇌와 생식소에서도 preproghrelin 유전자 발현이 확인되었는데, 이것은 HPG 축에서 ghrelin이 국부적인 역할을 담당할 가능성을 시사한다. 비록 뇌하수체에서의 기능은 아직 확실치 않지만, ghrelin은 시상하부의 GnRH, 뇌하수체의 생식소자극호르몬과 생식소의 성 스테로이드 호르몬 분비에 대한 음성적인 조절자로서의 역할을 수행하는 것으로 보인다. 최근의 연구들은 사춘기 개시, 그리고 아마도 폐경기 진입의 조절에서 ghrelin의 관여를 시사한다. 이제 ghrelin이 '뇌-위장관' 축의 필수적인 호르몬 요인이며, 신 진 대사와 생식 사이를 연결하는 조절 물질이라는 가능성은 매우 높다. '배부름'을 반영하는 leptin 신호와는 정반대인 ghrelin 신호는 신체 에너지 균형 상태로 볼 때 '배고픔'을 표현하는 것으로 생각되며, 항상성의 유지에서 최우선 사항으로 고려되지 않는 생식으로의 에너지 투자가 이루어지지 않도록 하는데 필수적일 것으로 사료된다. 생식능력 조절에 있어서 ghrelin의 보다 명확한 작용 메커니즘과 역할에 대한 깊은 통찰력을 얻고 성공적인 생의학적 적용을 위해서는 향후 더 많은 연구들이 필요하다.