• Title, Summary, Keyword: Leptin

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

  • 김명신;양현원;권혁찬;김세광;조동체;윤용달
    • Development and Reproduction
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    • v.6 no.2
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    • pp.123-129
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    • 2002
  • Leptin, a product of the obese gene, is associated not only with obesity but also with female reproductive function, but it has not yet been ascertained whether leptin acts directly on the ovary or indirectly via the hypothalamus-pituitary pathway. Therefore, the object of this study was to investigate the expession of leptin and its receptor in the rat ovary by immunohistochemistry and RT-PCR during the estrous cycle. Immunohistochemistry results showed that leptin was stained in the theca cells and in part of granulosa cells in atretic follicles, whereas leptin receptor was localized in the interstitial cells and ova in preantral follicies. In particular, leptin and its receptor in atretic follicles displayed more intensive staining compared to those in normal follicles. During the estrous cycle, the mRNA expression of leptin and its receptor in the ovary was detected by RT-PCR and estradiol, progesterone, and leptin levels in the serum was measured by ELISA. The leptin level in the serum on metestrous phase was significantly higher than that on estrous phase. Similar to leptin level, progesterone level increased on metestrous phase. Leptin mRNA was not detected throughout the estrous cycle, whereas leptin receptor mRNA was expressed on all phases of estrous cycle excepting the diestrous phase. These results suggest that leptin might be directly involved in the regulation of ovarian function in rat.

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

  • 김명신;양현원;권혁찬;황경주;윤현숙;박금자;김세광;윤용달
    • Development and Reproduction
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    • v.2 no.2
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    • pp.173-178
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    • 1998
  • Leptin, the product of the obese gene, is produced by adipose tissue and is known to be a hormone concerned with regulation of appetite and metabolism. Recent reports have shown that leptin is associated not only with obesity but also with female reproduction, but it has not yet been ascertained whether leptin acts directly on the ovaries or indirectly via the hypothalamus or pituitary pathway. The object of this study is to determine the expression of leptin and its receptor in the ovaries of 3 and 8 weeks old rats by immunohistochemistry and RT-PCR. In the ovaries of 3 and 8 weeks old rats, leptin was stained in the theca cells and portions of granulosa cells of atretic follicles, whereas leptin receptors was stained in interstitial cells and ova of preantral follicles. The RT-PCR results showed that leptin receptor mRNA was expressed in the ovaries of both immature and adult rats, while leptin mRNA was not. In conclusion, leptin mRNA was not expressed in the ovaries, however, leptin was detected by immunohistochemistry. Compared to leptin itself, leptin receptors in the ovaries were ascertained by both RT-PCR and immunohistochemistry. These results suggest that leptin is related to the regulation of the physiological functions of the ovaries.

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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.

Improvement of Leptin Resistance (렙틴 저항성의 개선)

  • Kim, Yong Woon
    • 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.

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

  • 김은정;정인철;오상환;조무연
    • Journal of Life Science
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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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The Relationship between Serum Leptin Concentration and Obesity Indices in a Rural Population (일부 농촌지역 주민의 혈청 leptin 농도와 비만지표의 관련성)

  • Shin, Min-Ho;Park, Kyeong-Soo;Choi, Jin-Su;Kim, Sang-Yong
    • 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
  • Objective : To evaluate the relationship between serum leptin concentration and obesity indices in a rural population. Methods : Two hundred and nine subjects were randomly sampled from 1036 residents who had participated in the survey. Their obesity indices were measured by bioelectrical impedance analysis and anthropometry. Serum leptin concentrations were measured by immunoradiometric assay. Results : Serum leptin concentrations were positively correlated with body mass index, percent of body fat, fat mass, waist circumference, and hip circumference. Serum leptin concentrations were higher in obese or overweighted subjects than normal or thin subjects(8.5[0.9-31.4] compared with $2.7[0.1-12.0]{\mu}g/L$, p<0.01). Serum leptin concentrations were higher in women than men, even after an adjustment to body mass index$(\beta=4.183,\;p<0.01)$. According to body composition, serum leptin concentrations were more related with waist circumference in men, hip circumference in women. Conclusions : Serum leptin concentrations are positively correlated with obesity indices. Serum leptin concentrations are higher in obese subjects, in women, and more related with peripheral obesity. These findings support the hypothesis that human obesity is associated with leptin-resistance rather than leptin-deficiency.

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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.

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

  • Choi, Jin-Hee;Park, Ho-Sun;Lee, Tae-Yoon;Kim, Sung-Kwang;Kim, Hee-Sun
    • 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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Production of Leptin in E. coli and Its Effect on Glucose and Acetate Transport and Expression of Uncoupling Protein-2 Gene in Adipose Tissues of Korean Cattle (Hanwoo)

  • Kim, K.S.;Baik, M.G.
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.8
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    • pp.1062-1068
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    • 2004
  • Leptin has a major role in the regulation of food intake and energy homeostasis. In addition, leptin participates in many physiological functions including regulation of lipid metabolism. Bovine recombinant leptin protein was produced in E. coli cells in order to understand function of leptin in the regulation of lipid metabolism. The leptin expression vector was constructed in pGEX-4T-3 vector and transformed into E. coli BL21 cells. Expression of the GST-leptin fusion protein was induced with IPTG. The fusion protein was purified using glutathione sepharose 4B batch method, and the recombinant leptin was eluted after thrombin protease digestion. The effect of leptin on glucose transport was examined in the differentiated adipocytes of 3T3-L1 cells. Leptin had no effect on basal and insulin-stimulated glucose transport in 3T3-L1 cells (p>0.05). Effect of recombinant leptin on glucose and acetate transport was examined in adipose tissues of Korean cattle (Hanwoo). Insulin stimulated glucose transport in both intramuscular and subcutaneous adipose tissues (p<0.05), but leptin did not affect glucose transport in both adipose tissues (p>0.05). Insulin stimulated acetate transport in bovine adipose tissues (p<0.05), but leptin did not affect acetate transport (p>0.05). Northern and RT-PCR analyses showed that mRNA levels of uncoupling protein-2 were increased by leptin treatment in 3T3-L1 cells without statistical difference (p>0.05). In conclusion, bovine recombinant leptin did not affect glucose and acetate transport in both 3T3-L1 adipocytes and bovine adipose tissues, while it stimulates UCP-2 mRNA expression in 3T3-L1 cells.

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.