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

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

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

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

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

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

BACKGROUND: Many studies have recently shown that leptin can promote angiogenesis via endothelial leptin receptors and induce oxidative stress in endothelial cells; These findings suggest the relationship between cardiovascular risk and blood leptin concentration. In the present study, we investigated the relationship between leptin concentration and carotid intima-medial thickness (CIMT) as an indicator of early atherosclerosis in adults. METHEODS: The study subjects comprised 138 (45 men and 93 women; mean age 42.4+/-7.5 years; mean BMI 24.0+/-2.7 kg/m2) without history of diabetes, hypertension or cardiovascular disease. We measured CIMT by high resolution ultrasonography and plasma leptin levels by radioimmunoassay. RESULTS: 1) No significant differences in age, BMI or CIMT between male and female subjects were noted, but the leptin levels in female were significantly higher than those in males. (8.42+/-5.90 ng/mL vs. 3.08+/-1.00 ng/mL, p<0.001) 2) CIMT showed a significant positive correlation with age (r=0.31, p< 0.001), BMI (r=0.25, p<0.01) and level (r=0.42, p<0.05) in simple regression analysis. 3) When male and female subjects were each divided into 3 groups by leptin concentration, no significant difference in CIMT among female subjects was found. In male subjects, CIMT was significantly higher in the highest tertile of leptin level than in the other 2 groups (0.65+/-0.03 mm vs. 0.56+/-0.07 mm and 0.53+/-0.07 mm, p<0.01) after adjustment for BMI and age. However, this difference was not significant after adjustment for smoking. 4) CIMT (0.61+/-0.05 mm vs. 0.53+/-0.07 mm, p<0.01) and leptin concentrations (3.57+/-2.13 ng/mL vs. 2.20+/-1.39 ng/mL, p<0.05) were significantly higher in male smokers than in male non-smokers. CONCLUSION: Our results demonstrated significant correlation of CIMT to plasma leptin level before adjustment for smoking. A possible explanation is the permissive action of smoking on the atherogenic effect of leptin. However, further studies to elucidate the relationships and interactions among smoking, leptin level and the development of atherosclerosis will be needed.
Adult* ; Atherosclerosis ; Cardiovascular Diseases ; Endothelial Cells ; Female ; Humans ; Hypertension ; Leptin* ; Male ; Oxidative Stress ; Plasma* ; Radioimmunoassay ; Receptors, Leptin ; Smoke ; Smoking ; Ultrasonography

PURPOSE: The adipocyte-derived cytokine leptin plays a major role in the control of stable body weight by suppressing food intake and increasing energy metabolism. Leptin regulates the cell proliferation of various epithelial cells and it may be involved in the promotion of cancer. Leptin and its receptor are highly expressed in gastric adenocarcinoma, but the association between the serum leptin level and the tissue expression of leptin is uncertain. We evaluated the serum leptin level and the expressions of leptin and leptin receptor in gastric cancer, and we explore the possible mechanism and role of leptin in the carcinogenesis of gastric cancer. MATERIALS AND METHODS: 72 carcinomas that were curatively resected at our hospital from October 2005 to March 2007 were included in this study. By immunoassay and immunohistochemical staining, we evaluated the serum leptin level and the expressions of leptin and its receptor, and we analyzed their relationship together with the clinicopathological variables. RESULTS: The serum leptin level was increased as the patient's BMI increased and it was decreased in H. pylori infected patients. The expression of leptin was increased as the TNM stage increased (P=0.014), and the expression of leptin receptor in the intestinal type gastric adenocarcinoma was higher than that in the diffuse type gastric adenocarcinoma (71.4% vs 28.6%, respectively, P=0.033). CONCLUSION: There was no significant correlation between the serum leptin level and expression of leptin in gastric cancer patients. The expression of leptin was associated with the TNM stage, but its role in the pathogenesis of gastric cancer has to be elucidated.
Adenocarcinoma ; Body Weight ; Cell Proliferation ; Eating ; Energy Metabolism ; Epithelial Cells ; Humans ; Immunoassay ; Leptin ; Receptors, Leptin ; Stomach ; Stomach Neoplasms

Carcinoma, Hepatocellular ; pathology ; Humans ; Leptin ; genetics ; Liver Neoplasms ; pathology ; RNA, Messenger ; genetics ; Receptors, Leptin ; genetics ; Tumor Cells, Cultured