• 제목, 요약, 키워드: Leptin

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흰쥐의 발정주기동안 난소내 Leptin 및 Leptin 수용체 발현의 주기적 변화에 관한 연구 (Study on the Cyclic Change of Leptin and Its Receptor Expression during the Estrous Cycle of Rat)

  • 김명신;양현원;권혁찬;김세광;조동체;윤용달
    • 한국발생생물학회지:발생과생식
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    • v.6 no.2
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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.

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흰쥐 난소내 Leptin 및 Leptin 수용체의 발현 (Expression of Leptin and Its Receptor in Rat Ovary)

  • 김명신;양현원;권혁찬;황경주;윤현숙;박금자;김세광;윤용달
    • 한국발생생물학회지:발생과생식
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    • v.2 no.2
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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.

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Roles of Leptin in Cancer Progression

  • Kang, Yu-Jin;Moon, A-Ree
    • Biomolecules & Therapeutics
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    • v.18 no.4
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    • pp.363-374
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    • 2010
  • Growing evidence suggests a prominent role for leptin in human cancer progression. The intricate pattern of leptin cross-talk with other associated signaling pathways is a critical area of research that will ultimately contribute to comprehending the role of leptin in cancer progression. This review summarizes a portion of the current understanding of leptin signaling, with a critical focus on its contribution to tumor cell invasion and metastasis. Five topics are addressed in this review: (1) Leptin receptor, (2) Leptin signaling, (3) Leptin and cancer, and (4) Leptin and tumor invasion. Due to the complex cellular effects of leptin, a more precise understanding of leptin signaling pathways must still be elucidated. Leptin is clearly a major factor for stimulating tumor progression through a complex spectrum of interplay and cross-talk among various signaling molecules. An understanding of the role of leptin in invasion and metastasis will provide valuable information for establishing strategies to modulate leptin signaling, which should be a high priority for the development of anti-cancer therapeutics.

렙틴 저항성의 개선 (Improvement of Leptin Resistance)

  • 김용운
    • Yeungnam University Journal of Medicine
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    • v.30 no.1
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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.

Dexamethasone and Acetate Modulate Cytoplasmic Leptin in Bovine Preadipocytes

  • Yonekur, Shinichi;Hirota, Shohei;Tokutake, Yukako;Rose, Michael T.;Katoh, Kazuo;Aso, Hisashi
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.4
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    • pp.567-573
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    • 2014
  • Hormonal and nutrient signals regulate leptin synthesis and secretion. In rodents, leptin is stored in cytosolic pools of adipocytes. However, not much information is available regarding the regulation of intracellular leptin in ruminants. Recently, we demonstrated that leptin mRNA was expressed in bovine intramuscular preadipocyte cells (BIP cells) and that a cytoplasmic leptin pool may be present in preadipocytes. In the present study, we investigated the expression of cytoplasmic leptin protein in BIP cells during differentiation as well as the effects of various factors added to the differentiation medium on its expression in BIP cells. Leptin mRNA expression was observed only at 6 and 8 days after adipogenic induction, whereas the cytoplasmic leptin concentration was the highest on day 0 and decreased gradually thereafter. Cytoplasmic leptin was detected at 6 and 8 days after adipogenic induction, but not at 4 days after adipogenic induction. The cytoplasmic leptin concentration was reduced in BIP cells at 4 days after treatment with dexamethasone, whereas cytoplasmic leptin was not observed at 8 days after treatment. In contrast, acetate significantly enhanced the cytoplasmic leptin concentration in BIP cells at 8 days after treatment, although acetate alone did not induce adipocyte differentiation in BIP cells. These results suggest that dexamethasone and acetate modulate the cytoplasmic leptin concentration in bovine preadipocytes.

대장균 세포에서 Leptin 유전자의 발현 유도 (Induction of Leptin cDNA Expression in Esherichia coli Cells)

  • 김은정;정인철;오상환;조무연
    • 생명과학회지
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    • v.9 no.3
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    • pp.253-261
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    • 1999
  • Leptin gene, an obesity gene, has been known to involve in the regulation of food intake and body weight. It is also thought to be related to the glucose metabolism, insulin secretion and type II diabetes mellitus. Recently, the production of recombinant leptin protein has been attempted for the application in the treatment of obesity and the correction of hereditary obesity and type II diabetes. In the present study, leptin cDNA was cloned from mouse fat cells by RT-PCR and prokaryotic expression of leptin was attempted in order ot prepare a leptin-specific antigen. Immunization of a rabbit with the leptin-specific antigen into a rabbit resulted in the generation of leptin-specific antiserum that could be useful in the detection of leption expressed in various tissues. The sequence of leptin cDNA prepared in the present study wa identical to the previously reported one. Transformation of E. coli(DH5a) cells with the leptin cDNA-inserted translation vector, pGEX-4T-3-leptin followed by treatment with IPTG (0.1mM) resulted in the expression of a large amount of GST-leptin fusion protein with a molecular weight of 44 KDa as an inclusion body. Denaturation of the insoluble fusion protein by 8M urea, 6M guanidium-HCI or 0.1% 2-mercaptoethanol followed by a slow oxidation could not solubilize the inclusion body. The cell extract was subjected to SDS-PAGE and GST-leptin protein electroeluted from the gel was then injected into a rabbit subcutaneously for the immunization. Anti-GST-leptin rabbit antiserum which had a cross reactivity to the GST-leptin protein was generated. Leptin protein expressed in mouse brain and fat tissues was detected by Western blot immunodetection system using the antiserum generated in the present study.

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일부 농촌지역 주민의 혈청 leptin 농도와 비만지표의 관련성 (The Relationship between Serum Leptin Concentration and Obesity Indices in a Rural Population)

  • 신민호;박경수;최진수;김상용
    • Journal of Preventive Medicine and Public Health
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    • v.33 no.2
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    • pp.193-198
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    • 2000
  • 일부 농촌지역 주민을 대상으로 혈청 leptin농도와 비만지표의 관련성을 파악하고자 하였다. 역학조사에 참여한 주민 1036명 중 단순무작위표본추출하여 혈청 leptin 농도를 측정한 209명을 연구대상으로 하였다. 체질량지수, 체지방량 등의 비만지수는 신체계측, 생체전기저항분석법으로 측정하였으며 혈청 leptin농도는 면역 방사계수측정 법으로 측정하였다. 혈청 leptin농도는 비만지표인 체질량 지수, 체지방률, 체지방량, 허리둘레, 엉덩이둘레와 유의한 양의 상관관계가 있었다. 혈청 leptin농도는 과체중 또는 비만인에서 저체중 또는 정상인보다 유의하게 더 높았다. 혈청 leptin농도는 남자보다 여자에서 더 높았는데 체질량지수를 보정한 상태에서도 남자보다 여자에서 더 높았다. 혈청 leptin 농도는 남자에서는 허리둘레, 여자에서는 엉덩이둘레와 더 관련이 있어 높은 혈청 leptin농도는 남자에서는 복부형 비만, 여자에서는 둔부형 비만과 관련이 있는 것으로 나타났다. 본 연구에서 혈청 leptin 농도는 비만지표들과 양의 상관관계가 있었고, 정상인보다 비만인, 남자보다 여자에서 더 높았으며, 복부형 비만보다 둔부형 비만과 더 관련이 있었다. 이러한 결과는 비만이 leptin결핍보다는 leptin 저항성과 더 관련이 있다는 가설을 지지하는 것이다.

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HER2 induces expression of leptin in human breast epithelial cells

  • Cha, Yujin;Kang, Youjin;Moon, Aree
    • BMB Reports
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    • v.45 no.12
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    • pp.719-723
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    • 2012
  • A close association between the obesity hormone leptin and breast cancer progression has been suggested. The present study investigated the molecular mechanism for enhanced leptin expression in breast cancer cells and its functional significance in breast cancer aggressiveness. We examined whether leptin expression level is affected by the oncoprotein human epidermal growth factor receptor2 (HER2), which is overexpressed in ~30% of breast tumors. Here, we report, for the first time, that HER2 induces transcriptional activation of leptin in MCF10A human breast epithelial cells. We also showed that p38 mitogen-activated protein kinase signaling was involved in leptin expression induced by HER2. We showed a crucial role of leptin in the invasiveness of HER2-MCF10A cells using an siRNA molecule targeting leptin. Taken together, the results indicate a molecular link between HER2 and leptin, providing supporting evidence that leptin represents a target for breast cancer therapy.

THP-1 세포주에서 Leptin에 의한 케모카인 유전자 발현 (Effect of Leptin on the Expression of Chemokine Genes in THP-1 Cells)

  • 최진희;박호선;이태윤;김성광;김희선
    • Yeungnam University Journal of Medicine
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    • v.20 no.2
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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.

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Development of Bovine Specific Leptin Radioimmunoassay and Relationship of Plasma Leptin with Vitamin A and Age of Wagyu

  • Yang, S.H.;Kawachi, H.;Khan, M.A.;Lee, S.Y.;Kim, H.S.;Ha, Jong K.;Lee, W.S.;Lee, H.J.;Ki, K.S.;Kim, S.B.;Sakaguchi, S.;Maruyama, S.;Yano, H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.9
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    • pp.1286-1295
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    • 2008
  • Leptin is produced by adipocytes and its role in the regulation of lipid metabolism, feed intake, productive and reproductive performance of domestic animal species has been greatly stressed and extensively investigated in recent years. This study was conducted to develop a radioimmunoassay (RIA) for the estimation of plasma bovine leptin and to determine plasma leptin concentration in fattening Japanese Black cattle (Wagyu) and its crossbreds at commercial farms. Relationships of plasma leptin with plasma vitamin A and age of crossbred cattle were also determined. Recombinant bovine leptin (rbleptin) was produced by the E. coli overexpressed leptin as a GST (glutathione S-transferase)-fusion protein. Then antiserum against bovine leptin was obtained by its immunization in rabbits. Using this antiserum, a bovine specific RIA was developed and plasma leptin level was determined in 120 crossbred fattening cattle (WagyuHolstein, 50:50) at commercial farms. The plasma leptin level increased with the age of cattle and its level was greater in the crossbred heifers than in the steers. Plasma vitamin A level was negatively correlated with plasma leptin level in crossbred heifers and steers. This relationship was stronger in heifers than in steers. Plasma leptin was gradually increased with advancing age in fattening Wagyu cattle. In conclusion, development of a bovine specific RIA to estimate plasma leptin will contribute to better understanding of the role of leptin in cattle.