Leptin is a versatile 16 kDa peptide hormone, with tertiary structure resembling that of members of the long-chain helical cytokine family. It is mainly produced by adipocytes in proportion to fat size stores, and was originally thought to act only as a satiety factor. However, the ubiquitous distribution of leptin receptors in almost all tissues underlies the pleiotropism of leptin. This review will focus on the link between leptin, a cytokine that is elevated in obese individuals, and cancer development through clarifying the intracellular signaling pathways of leptin. First, I discuss the biological functions of leptin and its signaling pathways. Then, I summarize the effects of leptin on different cancer types in experimental cellular and animal models. Next, I analyze the relationship between obesity and the presence of cancer or cancer risk in patients. Finally, leptin as a target for cancer treatment in the future and prevention will be discussed.
Adipocytes ; Carcinogenesis ; Humans ; Leptin ; Models, Animal ; Obesity ; Receptors, Leptin

PURPOSE: Leptin is a multifunctional hormone that's produced by adipose tissue and leptin is involved in the regulation of food intake and energy balance. The aims of this study were to determine the leptin and leptin receptor (Ob-R) expressions in human breast cancer and their corresponding influence on the prognosis of patients with breast cancer. MATERIALS AND METHODS: We examined the correlations between the leptin and Ob-R expressions and the breast cancer-related pathobiologic markers by performing immunohistochemistry in 517 patients with breast cancer. We analyzed the leptin and Ob-R expressions with respect to overall survival and relapse-free survival (RFS). RESULTS: Positive cytoplasmic immunoreactivity for leptin was noted in 39% of the patients and 79% of the patients showed positive cytoplasmic immunoreactivity for Ob-R. The expression of leptin in breast cancer was correlated with a high Ki-67 labeling index (p=0.019). Based on the univariate survival analysis, the clinicopathologic variables with prognostic value included the histologic grade, the T stage, the N stage, the HER2 status, the Bcl-2, p53 and Ki-67 expressions (p<0.05). The patients with leptin-positive breast cancers and a negative hormone receptor status had a significantly longer overall survival (p=0.021). Multivariate survival analysis showed that a positive expression of leptin was an independent prognostic marker for overall survival (hazard ratio, 0.20; 95% CI, 0.04~0.99; p=0.05). CONCLUSION: A leptin expression in breast cancer is significantly associated with the Ki-67 labeling index, and this suggests there is an association of a leptin expression with the proliferation activity. In addition, a leptin expression is an indicator of better survival for breast cancer patients.
Adipose Tissue ; Breast ; Breast Neoplasms ; Cytoplasm ; Eating ; Humans ; Immunohistochemistry ; Leptin ; Prognosis ; Receptors, Leptin

No abstract available.
Animals ; Clone Cells* ; Cloning, Organism* ; DNA, Complementary* ; Leptin* ; Rats* ; Receptors, Leptin*

OBJECTIVEConditioned taste preference (CTP) is a taste learning reflex by which an animal learns to prefer a substance which tastes not well and has been studied with much interest in recent years. However, the neural substrates of CTP are less known. This study aimed to determine the possible neural path- ways of CTP and whether serum leptin level and the leptin receptor (OB-Rb) in the hind brain are involved following CTP formation.

METHODSWe established CTP of quinine in rats with a 2-bottle preference test. The serum leptin concentrations were detected, the expression of c-fos in the rat brain was tested to determine the nuclei in relation with establishment of CTR Finally, the OB-Rb mRNA expression was examined by RT-qPCR assay in parabrachial nucleus (PBN) and the nucleus of the solitary tract (NST) of the hind brain.

RESULTSCompared with control group, the level of serum leptin was higher in the CTP group (4.58 ± 0.52 vs 1.67 ± 0.25 µg/L, P < 0.01); increased c-fos positive cells were found in the anterior hypothalamus (AH, 221.75 ± 4.96 vs. 178.50 ± 6.63 cells/mm², P < 0.05), the basal lateral amygdala (BLA, 70.75 ± 6.17 vs 56.50 ± 3.62 cells/ mm², P < 0.05) and the nucleus of the solitary tract (NST, 41.25 ± 1.32 vs 32.50 ± 1.02 cells/mm², P < 0.05). But in ventromedial nucleus of the hypothalamus (VMH, 20.75 ± 2.73 vs 38.5 ± 1.54 per 1 mm², P < 005), PBN (21.50 ± 2.24 vs 36.25 ± 1.49 cells/mm², P < 0.05) and the central nucleus of the amygdala (CeA, 22.25 ± 1.53 vs 35.50 ± 2.11 cells/mm², P < 0.05), the number of c-fos positive cells was decreased in the CTP group. In addition, we found OB-Rb mRNA expression in PBN of CTP group rats was higher than that of control group (0.95 ± 0.055 vs 0.57 ± 0.034, P < 0.05), while there was no significant difference of OB-Rb mRNA expression in NST between the two groups.

CONCLUSIONNuclei AH, BLA, NST, VMH, PBN and CeA participate in the formation of CTP. Leptin and its receptor in PBN may be involved in the formation and maintenance of CTP.

Animals ; Conditioning (Psychology) ; Leptin ; blood ; Rats ; Receptors, Leptin ; physiology ; Rhombencephalon ; physiology ; Taste ; physiology

Leptin, the product of obese gene, is a secreting protein that exerts multiple biological functions by binding to its receptor. Leptin regulates nutrient intake and metabolism, and is secreted from adipocytes, which occupy most of the bone marrow cavity and constitute the microenvironment. Leptin not only plays an important role in the control of the proliferation and differentiation of normal primitive hematopoietic cells, but it also stimulates the growth and viability of leukemic cells. Leukemic cells of some patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia, and chronic myeloid leukemia also express the leptin receptor. Furthermore, leptin also stimulates leukemic cell growth in vivo by promoting angiogenesis. These findings suggest the possibility that leptin and its receptor play roles in the pathophysiology of leukemia, and blockage of leptin binding to its receptor might have potential therapeutic benefits in the treatment of certain leukemias. This review discusses the biological characteristics of leptin and its receptor, the relation of leptin and its receptor with normal hematopoiesis, the relation of leptin and its receptor with AML and so on.
Animals ; Hematopoietic System ; Humans ; Leptin ; physiology ; Leukemia, Myeloid, Acute ; Receptors, Leptin ; physiology

Leptin, a 167-amino acid peptidic hormone encoded by the obese gene, is known to be involved in the regulation of body fat, energy expenditure, immune function, angiogenesis, inflammatory reaction, the onset of puberty, and the regulation of reproductive function. The roles of leptin vary with different expression and distribution patterns of its receptor Ob-R. This article analyzes the biological effects of leptin and its receptor on the testis by reviewing the expression and distribution of Ob-R in different cells during different developmental stages or in different physiological and pathological states in the testis of men, mice or rats.
Animals ; Humans ; Male ; Mice ; Rats ; Receptors, Leptin ; metabolism ; Testis ; metabolism

PURPOSE: Adipocytokines, such as leptin, resistin, and adiponectin, are associated with obesity and breast cancer. Several studies have indicated that adipocytokines may influence tumor growth or differentiation. The aims of this study were to determine the expression of leptin, leptin receptor (ObR), adiponectin and adiponectin receptor (AdipoR) in human breast cancer, to evaluate their prognostic significance in the breast cancer. METHODS: Specimens from 198 patients with primary breast cancer were enrolled, and representative paraffin tumor blocks were selected for constructing tissue microarrarys (TMA). Immunohistochemical staining for leptin, ObR, adiponectin, and AdipoR was performed using TMA, and the clinicopathologic characteristics were evaluated from the patient's medical records. RESULTS: Stage 0 breast cancer accounted for 41 cases, and 157 cases were invasive cancer. Positive rates of leptin and ObR expression in the ductal carcinoma in situ (DCIS) group were significantly higher than those of the invasive cancer group (97.4% vs. 34.0%, p<0.001; 74.4% vs. 29.8%, p<0.001). However, positive rates of adiponectin and AdipoR expression in the invasive cancer group were significantly higher than those in the DCIS group (53.7% vs. 33.3%, p=0.024; 59.9% vs. 26.3%, p<0.001). High leptin expression was significantly associated with high Ki-67 expression (p=0.016). High adiponectin expression was significantly correlated with smaller tumor size (p=0.001). CONCLUSION: We suggest that losses of leptin and ObR expression could be associated with invasive cancer, whereas high adiponectin and AdipoR expression may be associated with breast cancer invasiveness.
Adipokines ; Adiponectin ; Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Humans ; Leptin ; Obesity ; Paraffin ; Receptors, Adiponectin ; Receptors, Leptin ; Resistin

OBJECTIVE: The potential role of leptin as an endocrine regulator is unknown in ovarian cancer. In the present study, we investigated the expression of letpin receptors in IOSE (Immortalized ovarian surface epithelium) and ovarian cancer cell lines, and potential role of leptin on the cell growth and taxol induced apoptosis. METHODS: To check the presence of leptin receptors in 4 human epithelial ovarian cancer cell lines (SK-OV-3, R182, A2780 and CP70), RT-PCR was done. In the RT-PCR, 2 primers were used; primers for short form of leptin receptor and for long form of leptin receptor. Cancer cell lines were treated with leptin and the cell viability was measured using the cellTiter 96 Aqueous One Solution Cell Proliferation Assay Kit. The antiapoptotic effect of leptin against taxol induced apoptosis on ovarian cancer cell lines was evaluated by checking caspase 3/7 activity. RESULTS: Leptin receptors on ovarian cancer cell lines were expressed differentially according to the type of isoform. There was long form leptin receptor on CP70, but no short form receptor. All other cell line showed both short and long form receptors. Leptin increased cell viability in all cell lines in a dose-dependent manner and reduced the number of apoptotic cells in A2780. CONCLUSIONS: There were leptin receptors in IOSE and some ovarian cancer cell lines. Chronic increase in leptin concentration may enhance the growth of ovarian cancers. In part, the increased cell growth after leptin treatment seemed to be due to the antiapoptotic effect of leptin.
Apoptosis ; Cell Line ; Cell Proliferation ; Cell Survival ; Humans ; Leptin ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Paclitaxel ; Receptors, Leptin

PURPOSE: Leptin is a potent adipokine that plays a significant role in tumor development and the progression of breast cancer. The aim of this study was to evaluate whether leptin affects the response to tamoxifen treatment in estrogen receptor (ER)-positive breast cancer cells. METHODS: Leptin, leptin receptor (Ob-R), and activation of signaling pathways were studied by Western immunoblotting. The effects of leptin on tamoxifen-dependent growth inhibition were studied in MCF-7 and T-47D cells. RESULTS: Leptin was expressed in MCF-7 and T-47D and had a proliferative effect on MCF-7 cells. Leptin significantly inhibited the antiestrogenic effect of tamoxifen in both cells only under beta-estradiol (E2) (20 nM) conditions. In MCF-7, the inhibitory effect against tamoxifen was a result from the activation of the ERK1/2 and STAT3 signal transduction pathway. CONCLUSION: Leptin interferes with the effects of tamoxifen under E2 stimulated conditions in ER-positive breast cancer cells. These results imply that inhibition of leptin is expected to enhance the response to tamoxifen in ER-positive breast cancer cells, and, therefore, could be a promising way to overcome endocrine resistance.
Adipokines ; Blotting, Western ; Breast ; Breast Neoplasms ; Estrogen Receptor Modulators ; Estrogens ; Leptin ; MCF-7 Cells ; Receptors, Leptin ; Signal Transduction ; Tamoxifen

OBJECTIVE: To verify the expression of leptin receptor (OB-R) in oocytes and preimplantation embryos, the involvement of mitogen activated protein kinase (MAPK or Erk1/2) in the leptin signaling, and effect of leptin on the oocyte maturation in mice. METHOD: RT-PCR analysis of OB-R was conducted in germinal vesicle (GV)-intact and MII stage oocytes, and 1, 2, 8-cell embryos and blastocysts. Germinal vesicle breakdown (GVB), polar body extrusion, monitored in the presence or absence of leptin (1 microM). Following the leptin treatment, temporal changes in MAPK activity were verified by immunoprecipitation and in vitro kinase assay in MII oocytes. RESULTS: The expression of OB-R mRNA was found in GV and MII oocyte but not in the embryos. MAPK activity of the MII oocytes was significantly increased by brief incubation in the HTF supplemented with leptin (1 microM). Priming of PD098059, a MEK inhibitor to leptin treatment attenuated the activation of MAPK by leptin in MII oocytes. Following 24 hrs of culture of the GV oocytes, leptin significant increased the GVB and 1st polar body extrusion. CONCLUSION: This result suggested that functional interaction between leptin and OB-R resulted in potentiation of MAPK (Erk1/2) activity in MII oocytes through MEK activation and that leptin might be a local regulator of meiotic maturation of the mouse oocytes.
Animals ; Blastocyst ; Embryonic Structures ; Immunoprecipitation ; Leptin* ; Mice* ; Oocytes* ; Phosphotransferases ; Polar Bodies ; Protein Kinases* ; Receptors, Leptin ; RNA, Messenger