• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.722-729
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• 2004

Leptin is an adipocyte-secreted hormone and its plasma levels correlate with total body fat mass, however, it also plays a regulatory role in immunity, inflammation, and hematopoiesis. Chemokine is known as a chemoattractant cytokine in inflammatory reaction, but its role in leptin reaction has not been well studied. In this study, the direct effect of leptin on the expression of chemokine mRNAs and lipopolysaccharide (LPS)-induced chemokine KC mRNA in mouse peritoneal macrophages was investigated. Leptin did not induce the expression of lymphotactin, RANTES, eotaxin, MIP-1$\beta$, MIP-1$\alpha$, MIP-2, MCP-1, IP-10, TCA-3, and KC mRNA in mouse peritoneal macrophages, and had no direct effect on the expression of these LPS-induced chemokine mRNAs except KC mRNA. The synergistic effect of leptin on the expression of LPS-induced KC mRNA occurred late in the time course of response to LPS. The increased expressions of Ob-Rb mRNA and leptin receptor protein were detected during the LPS treatment. Leptin produced a substantial increase in the stability of the LPS-induced KC mRNA, and the synergistic effect of leptin on LPS-induced KC mRNA expression was further augmented by cycloheximide (CHX). Pyrrolidine dithiocarbamate (PDTC) did not block the synergistic effect of leptin on LPS-induced KC mRNA expression in mouse peritoneal macrophages. These data suggest that although leptin has no direct effect on the expression of lymphotactin, RANTES, eotaxin, MIP-1$\beta$, MIP-1$\alpha$, MIP-2, MCP-1, IP-10, TCA-3, and KC mRNA in mouse peritoneal macrophages, the synergistic effect of leptin on the expression of LPS-induced KC mRNA has the possibility that LPS might induce the expression of the Ob-Rb receptor or an unknown gene(s) that sensitizes macrophages to the synergistic function of leptin. Therefore, further studies are necessary to examine leptin as a regulatory factor of chemokine production.

• 한국발생생물학회지:발생과생식
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• 제2권2호
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• pp.173-178
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• 1998

비만유전자 산물인 leptin은 지방 조직에서 생성되어 혈액으로 분비되며, 신진대사, 식욕, 체열 등을 조절하여 비만의 억제 조절 물질로 작용하는 것으로 알려져 있다. 또한 leptin은 비만 뿐만 아니라 생식 생리와도 관련이 있는 것으로 보이며, 이러한 leptin의 작용이 난소에 직접적인지 혹은 시상하부나 뇌하수체를 매개로 하는지는 아직 정확하게 밝혀지지 않고 있으며, 난소에서의 leptin 및 leptin 수용체의 발현 양상에 대한 연구 또한 미진한 상태에 있다. 따라서 본 연구는 생후 3주령과 8주령의 흰쥐 난소에서 leptin과 leptin 수용체의 발현 양상을 면역조직화학방법과 RT-PCR 방법으로 조사하였다. 면역조직화학방법 결과 3주령과 8주령 흰쥐 모두에서 leptin은 협막세포와 폐쇄 난포의 일부 과립세포에 염색되었고, leptin수용체는 협막세포, 간질세포와 난포강이 형성되지 않은 난포의 난자에 염색되었다 RT-PCR 결과 3주 및 8주 흰쥐 난소에서 leptin mRNA는 모두 발현되지 않은 반면, leptin 수용체 mRNA는 모두 발현되었다. 결론적으로 leptin mRNA가 난소에서 발현되지는 않지만, 면역조직화학방법으로 leptin의 발현을 확인하였고, leptin 수용체는 난소에서 RT-PCR 방법과 면역조직화학방법으로 모두 확인할 수 있었다. 이러한 결과로 보아 혈액에서 난소 내로 유입된 leptin이 협막세포, 간질세포와 난자의 leptin 수용체에 결합하여 난소의 생리적 기능을 조절할 수 있는 것으로 사료된다.

• 한국발생생물학회지:발생과생식
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• 제6권2호
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• pp.123-129
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• 2002

비만유전자 산물인 leptin은 비만뿐만 아니라 여성의 생식 생리와 관련이 있는 것으로 보이나, 아직 이러한 leptin이 난소에 직접적으로 작용하는지 정확하게 밝혀지지 않고 있다. 따라서 본 연구에서는 흰쥐 난소에서 leptin과 leptin 수용체의 발현을 면역조직화학방법으로 확인하고 발정주기에 따른 leptin과 leptin 수용체의 발현 양상을 RT-PCR 방법으로 조사하고자 하였다. 면역조직화학적 염색방법 결과 흰쥐 난소내에서 leptin은 협막세포와 폐쇄 난포의 일부 과립세포에 염색되었고, leptin 수용체는 협막세포, 간질세포와 난포강이 형성되지 않은 난포의 난자에 염색되었다. 특히 폐쇄 난포에서는 leptin과 leptin 수용체가 정상 난포에 비해 강하게 염색되었다. 흰쥐의 발정주기 동안 혈청내 estradiol, progesterone leptin의 농도는 ELISA 방법으로 측정하였고, 난소내 leptin과 leptin 수용체의 mRNA 발현 양상은 RT-PCR 방법으로 조사하였다. 혈중 leptin 농도를 측정한 결과 estrous 시기에 비하여 metestrous 시기에 유의하게 증가하였고, 이 시기에 progesterone 농도가 함께 증가하는 것을 관찰할 수 있었다. Leptin mRNA는 모든 발정주기에서 발현되지 않았지만 leptin 수용체 mRNA는 diestrous 시기를 제외한 다른 발정주기에 모두 발현되었다. 이러한 결과는 leptin이 흰쥐 난소의 기능을 조절하는데 직접적으로 관여할 수 있다는 것을 제시하고 있다.

• Journal of Nutrition and Health
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• 제39권8호
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• pp.748-755
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• 2006

The purpose of this study was to find out effects of treatment of ginsenoside Re, Rc and EGCG on mRNA expressions of leptin, hormone sensitive lipase (HSL) and resistin in 3T3-L1 adipocytes. The concentrations of EGCG were treated with $0.01{\times}10^{-7},\;0.1{\times}10^{-7},\;1{\times}10^{-7}\;and\;1{\times}10^{-6}\;or\;100{\mu}g/ml$ ginsenoside Re, Rc in culture cell for 13 days. mRNA expression of leptin wasn't expressed in preadipocyte but according to differentiation of adipocyte, the that of mRNA expression was decreased at gensenosids or EGCG treated cells compared with non treated adipocyte. Expression of HSL mRNA was increased in G-Re, G-Rc and EGCG treated cells compared with non treated cells. The resistin level was significantly decreased in adipocytes treated with G-Re, G-Rc and EGCG. These pattern was similar to leptin expression. These results support that treatment of gensenosides or EGCG in 3T3-L1 adipocyte resulted to affect of leptin and resistin as well as HSL mRNA levels, accordingly, levels of leptin and HSL will be acted by signalling body fat stores to the hypothalamus which in turn regulates food intake andenergy expenditure to maintain body weight homeostasis. And also regulation of resistin mRNA will prevent to diabetics attacked with obesity. In conclusion, we suggest that consumption of ginseng saponine or EGCG might prevent human diabetics or/and obesity.

• 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.

• Journal of Yeungnam Medical Science
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• 제20권2호
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• pp.129-141
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• 2003

Background: Leptin is a 16-KDa non-glycosylated peptide hormone synthesized almost exclusively by adipocytes. The well-known function of leptin is regulation of food intake and energy expenditure. Leptin also plays a regulatory role in immune and inflammatory process including cytokine production. The purpose of this study was to investigate the effect of leptin on the expression of several chemokine genes(RANTES, IL-8, MCP-1, IP-10, Mig, MIP-$1{\alpha}$, MIP-$1{\beta}$, and GRO-${\alpha}$) in THP-1 cells. Materials and Methods: Total RNA of THP-1 cells were prepared by Trizol method, and then stimulated with the leptin(250 ng/$m{\ell}$) or LPS(100 ng/$m{\ell}$). We examined the expression patterns of various chemokine mRNAs in THP-1 cell lines by RT-PCR and Northern blot. Results: Leptin did not induce the expression of chemokine mRNAs in THP-1 cells. The expression patterns of RANTES, IL-8, MCP-1, IP-10, and Mig mRNAs in THP-1 cells stimulated with leptin and LPS simultaneously was almost same to the patterns of LPS alone-induced chemokine mRNAs. RANTES mRNA expression was independent on the concentrations of leptin. Although leptin did not have strong effect on the expression of RANTES, IL-8, MCP-1, IP-10, Mig, MIP-$1{\alpha}$, MIP-$1{\beta}$, and GRO-${\alpha}$ mRNAs in THP-1 cells, leptin could induce the expression of long isoform of leptin receptor(OB-RL) mRNA, and its expression was elevated in simultaneous stimulation of leptin and LPS. Conclusion: These data suggest that leptin is able to induce OB-RL in THP-1 cells, however, leptin has little effect on the expression of pro-inflammatory chemokine genes.

• 약학회지
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• 제42권6호
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• pp.589-597
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• 1998

Effects of Mori Folium Ethanol Soluble Fraction (MFESF) on mRNA expression of glucose transporters, acetyl-CoA carboxylase (ACC) and leptin were examined in db/db mice. 500 and 1000mg/kg dose for MFESF (designated by SY 500 and SY 1000, respectively) and 5mg/kg dose for acarbose were administered for 6 weeks. Quantitations of glucose transporters (GLUT-2 and GLUT-4), ACC and leptin mRNA were performed by RT-PCR and in vitro transcription with co-amplification of rat ${\beta}$-actin gene as an internal standard. Muscular GLUT-4 mRNA expression in MFESF-treated groups were increased dose dependently. On the other hand, MFESF caused the GLLT-4 and leptin mRNA expressions in adipose tissue to decrease dose dependently, which means that triglyceride synthesis in adipocytes might be decreased and consequently signals adipocytes to inhibit the synthesis and release of leptin. Hepatic ACC mRNA expression in MFESF-treated groups was also decreased. and this may result in lowering of serum triiglyceride level. In contrast, liver GLUT-2 mRNA expressions in MFESF-treated and acarbose groups were increased. Higher rate of glucose uptake into hepatocytes is known to inhibit a phosphoenolpyruvate carboxykinase (PEPCK)-catalyzed reaction, which is a rate-limiting step in gluconeogenesis.

• Asian-Australasian Journal of Animal Sciences
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• 제21권2호
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• pp.161-166
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• 2008

To determine if body weight change is directly related to altered leptin and neuropeptide Y (NPY) gene expression, we assessed adipose tissue weight, percent body fat, leptin and NPY mRNA levels and serum leptin concentration in pigs at weights of 1, 20, 40, 60, and 90 kg. The results indicated that the weight of adipose tissues and the percent body fat of pigs significantly increased and correlated with body weight (BW) from 1 to 90 kg (p<0.01). Serum leptin concentrations and leptin mRNA levels in omental adipose tissue (OAT) increased from 1 to 60 kg, and then decreased from 60 to 90 kg. At 60 kg, the serum leptin concentration and leptin mRNA level significantly increased by 33.5% (p<0.01) and 98.2% (p<0.01), respectively, as compared with the levels at 1 kg. At 60 kg, the amount of leptin mRNA in subcutaneous adipose tissue (SAT) was significantly higher than that of 1 and 40 kg animals (p<0.05). NPY gene expression in the hypothalamus also changed with BW and at 60 kg the NPY mRNA level significantly decreased by 54.0% (p< 0.05) as compared with that in 1 kg. Leptin mRNA in OAT was correlated with serum leptin concentrations (r = 0.98, p<0.01), body weight (r = 0.82, p<0.05) and percent body fat (r = 0.81, p<0.05). This is the first report of the developmental expression of leptin in porcine OAT, peritoneal adipose tissue (PAT) and SAT, and proves that the expression of leptin in OAT could reflect the levels of circulating leptin. These results provide some information for nutritional manipulation of leptin secretion which could lead to practical methods of controlling appetite and growth in farm animals, thereby regulating and improving efficiency of lean meat production and meat production quality.

• Preventive Nutrition and Food Science
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• 제9권4호
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• pp.336-341
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• 2004

Leptin, resisitn and PAI-1 (plasminogen activator inhibitor-1) are synthesized and secreted by rodent fat cells and recently postulated to be an important link to obesity. This study was conducted to characterize the hormonal regulation of leptin, resistin, and PAI-1 gene expression in the 3T3-L1 adipocytes. The cells were treated with 0.5 $\mu$M insulin, 1 $\mu$M dexamethasone (Dex), or 0.05 $\mu$M triiodothyronine (T3) for 72 hours. The mRNA levels of each peptide were measured by semi-quantitative RT-PCR. The mRNA level of the leptin-producing ob gene was significantly increased by insulin, Dex, and T3 by 3.2-, 3.1- and 2.7-fold, respectively, compared to the control (p < 0.05). The level of resistin mRNA was increased by insulin, Dex, and T3 by 2.7-, 2.5- and 2-fold, respectively, compared to the control (p < 0.05). Likewise, the level of PAI-1 mRNA was significantly increased by insulin, Dex, and T3 compared to the control (p < 0.05). Taken together, our results suggest that insulin, Dex, and T3 may regulate the gene expression of leptin, resistin, and PAI-1 in 3T3-L1 adipocytes.

• Nutritional Sciences
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• 제6권2호
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• pp.73-77
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• 2003

PAI-1 (plasminogen activator inhibitor-1), leptin, and resistin are synthesized and secreted by Int cells of rodents and have recently been postulated to be an important link to obesity. This study was conducted to identify the nutritional regulation of PAI-1, leptin, and resistin gene expression in 0b/ob mice. The mice were divided into four groups according to nutritional status: control, 48 hour fasting, 48 hour-fasting/12 hour-refeeding, and 48 hour-fasting/24 hour-refeeding. The mRNA levels of each peptide were measured by semi-quantitative RT-PCR. In visceral fat tissue, the level of PAI-1 mRNA increased markedly when 48h-fasted animals were refed with a high carbohydrate-low fat diet. However, lasting/refeeding did not appreciably change PAI-1 mRNA levels in subcutaneous fat tissue. Similar results were obtained for resistin mRNA levels in both types of fat tissues. These findings suggest that visceral adipose tissue might be more sensitively involved in the nutritional regulation of PAI-1 and resistin gene expression compared to subcutaneous fat tissue. The level of leptin mRNA decreased markedly in the 48h-fasted animals, and increased markedly when 48h-fasted animals were refed with a high carbohydrate-low fat diet. The nutritional regulation of leptin mRNA showed similar patterns in both types of fat tissues. In conclusion, the nutritional regulation of gene expression encoding PAI-1, resistin, and leptin from adipocytes may vary according to the type of adipose tissue.