• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6595-6599
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• 2013

Leptin and its receptor are involved in breast carcinogenesis as mitogenic factors. Therefore, they could be considered as targets for breast cancer therapy. Expression of the leptin receptor gene could be modulated by leptin secretion. Silibinin and curcumin are herbal compounds with anti-cancer activity against breast cancer. The aim of this study was to assess their potential to inhibit of expression of the leptin gene and its receptor and leptin secretion. Cytotoxic effects of the two agents on combination on T47D breast cancer cells was investigated by MTT assay test after 24h treatment. With different concentrations the levels of leptin, leptin receptor genes expression were measured by reverse-transcription real-time PCR. Amount of secreted leptin in the culture medium was determined by ELISA. Data were statistically analyzed by one-way ANOVA test. The silibinin and curcumin combination inhibited growth of T47D cells in a dose dependent manner. There were also significant difference between control and treated cells in leptin expression and the quantity of secreted leptin with a relative decrease in leptin receptor expression. In conclusion, these herbal compounds inhibit the expression and secretion of leptin and it could probably be used as drug candidates for breast cancer therapy through leptin targeting in the future.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.1
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• pp.1-6
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• 2006

To evaluate whether metformin restores leptin sensitivity in aged rats with leptin resistance, we measured leptin sensitivity in aged (2 year old) and adult (5 month old) rats after 4 weeks of treatment with metformin (300 mg/kg/D, mixing in drinking water), by measuring food intake, body weight and visceral fat losing effects. Leptin ($15{\mu}g/D$) was administered by intracerobroventricular (i.c.v.) infusion through osmotic minipump for 1 week. Metformin treatment decreased body weight and daily food intake in both adult and aged rats compared with their control rats, however, these effects were more prominent in aged rats than in adult rats. Anorexic and fat losing responses following i.c.v. leptin were attenuated in aged rats compared to adult rats. However, these responses of aged rats to leptin were restored by metformin treatment. Moreover, serum concentration of leptin in aged rats was significantly decreased by combined treatment with metformin and leptin. These results suggest that metformin enhances leptin sensitivity in aged rat model, and that combination therapy with metformin and leptin would be helpful for treatment of aging-associated obesity.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.487-498
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• 2016

Leptin, an adipokine predominantly produced from adipose tissue, is well known to induce tumor growth. However, underlying molecular mechanisms are not established yet. While p53 has long been well recognized as a potent tumor suppressor gene, accumulating evidence has also indicated its potential role in growth and survival of cancer cells depending on experimental environments. In the present study, we examined if p53 signaling is implicated in leptin-induced growth of cancer cells. Herein, we demonstrated that leptin treatment significantly increased p53 protein expression in both hepatic (HepG2) and breast (MCF-7) cancer cells without significant effect on mRNA expression. Enhanced p53 expression by leptin was mediated via modulation of ubiquitination, in particular ubiquitin specific protease 2 (USP2)-dependent manner. Furthermore, gene silencing of p53 by small interfering RNA (siRNA) suppressed leptin-induced growth of hepatic and breast cancer cells, indicating the role of p53 signaling in tumor growth by leptin. In addition, we also showed that knockdown of p53 restored suppression of caspase-3 activity by leptin through modulating Bax expression and prevented leptin-induced cell cycle progression, implying the involvement of p53 signaling in the regulation of both apoptosis and cell cycle progression in cancer cells treated with leptin. Taken together, the results in the present study demonstrated the potential role of p53 signaling in leptin-induced tumor growth.

• 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.

• Clinical and Experimental Reproductive Medicine
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• v.28 no.2
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• pp.111-120
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• 2001

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 ($1{\mu}M$). 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 ($1{\mu}M$). 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 1 st 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.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.3
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• pp.306-315
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• 2021

Purpose: Obesity is defined as the abnormal or excessive accumulation of fat over acceptable limits. Leptin is a metabolic hormone present in the circulation in amounts proportional to fat mass. Leptin reduces food intake and increases energy expenditure, thus regulating body weight and homeostasis. Various polymorphisms are present in the leptin gene and its receptor. These polymorphisms may be associated with obesity. This study aimed to show the association of leptin (+19) AG, leptin (2548) GA, and Gln223Arg leptin receptor polymorphisms with obesity and metabolic syndrome in Turkish children aged 6-17 years, and to conduct further investigations regarding the genetic etiology of obesity. Methods: A total of 174 patients diagnosed with obesity and 150 healthy children who were treated at Tokat Gaziosmanpasa Medical School Hospital between September 2014 and March 2015 were included in this study. The ages of the children were between 6 and 17 years, and anthropometric and laboratory results were recorded. Genotyping of leptin (+19) AG, leptin (2548) GA, and leptin receptor Gln223Arg polymorphisms was performed by polymerase chain reaction. Results: An association between leptin receptor Gln223Arg gene polymorphism and obesity was detected. Conclusion: Further studies are needed to determine the role of genetic etiologies and to indicate the role of leptin signal transmission impairment in the pathogenesis of obesity. We hope that gene therapy can soon provide a solution for obesity.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.3 no.2
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• pp.175-180
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• 2000

Purpose: Leptin is an adipocyte-derived blood-borne satiety factor that acts on its cognate leptin receptor in the hypothalamus, thereby regulating food intake and energy expenditure. We measured the leptin concentrations in serum of normal and obese children with human leptin ELISA kit, unlike previous study with leptin RIA kit and investigated the relationship between leptin concentrations and body mass index, gender, and age. Methods: We measured serum concentrations of leptin in 67 children who were visited to the Department of Pediatrics, Chungnam National University Hospital during the period of 5 months from February, 1999 to June, 1999. Height, weight, obesity index, and body mass index were measured in 67 subjects. Leptin values in serum were measured by sandwich ELISA method. Data analysis was done according to the obesity, body mass index, gender and age. Results: The mean concentration of leptin was $7.69{\pm}8.83\;ng/ml$ in normal children group and $36.34{\pm}18.57\;ng/ml$ in obese group. Serum leptin concentrations were significant correlation with the body mass index (p<0.01). Serum leptin concentration was significant higher in the group of over 10 years of age (p<0.01). Leptin levels showed no significant difference by gender. Conclusion: Serum leptin levels were significantly higher in obesity group than in control one, and they were correlated with body mass index and age. Measurements of leptin value by sandwich ELISA method are very useful and easily applicable to determine obesity.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.9 no.1
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• pp.48-57
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• 2006

Purpose: To investigate the correlation of the serum leptin, adiponectin, and leptin/adiponectin ratio with metabolic disorders in the childhood obesity. Methods: Fifty children (25 obese and 25 non-obese) were recruited in the pediatric outpatient clinic of Chosun University Hospital from January 1st to June 30th 2005. Adiponectin, leptin, anthropometric parameters, glucose, LDL-cholesterol, HDL-cholesterol, total cholesterol, triglyceride, and insulin levels were measured. The correlations of leptin and adiponectin levels with anthropometric parameters, glucose, insulin and lipids were analyzed by Pearson's correlation coefficients. Results: Insulin and leptin levels of the obese group were significantly higher than those of the non-obese group (p<0.05, p<0.001 respectively). HDL-cholesterol and adiponectin levels of the obese group were significantly lower than those of the non-obese group (p<0.005, p<0.05 respectively). In the obese group, leptin level was positively correlated with BMI and the percentage of body fat, but negatively correlated with adiponectin level. Moreover, adiponectin level of the obese group was negatively correlated with BMI and the percentage of body fat, but positively correlated with leptin level. In the non-obese group, only insulin level was positively correlated with adiponectin. In the obese group, leptin/adiponectin ratio was positively correlated with the percentage of body fat and leptin level. Also, leptin/adiponectin ratio was positively correlated with BMI and the percentage of body fat in the non-obese group. Conclusion: Leptin, adiponectin, and leptin/adiponectin ratio did not appear to have a major role linking various metabolic disorders in the childhood obesity, even though they were strongly associated with obesity indices. Also, leptin/adiponectin ratio was associated with obesity indices even in non-obese children.

• Journal of Nutrition and Health
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• v.35 no.7
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• pp.737-742
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• 2002

To evaluate the effect of obesity on serum leptin and insulin levels in 80 elementary school children (aged 10.8 yr, 47 boys, 33 girls), we collected the anthropometric data and measured serum leptin and insulin levels. Serum leptin level and insulin resistance are known as factors which are associated with obesity and obesity related diseases such as diabetes, cardiovascular disease, hypertension. The results were as follows. The serum levels of insulin (p＜0.001), leptin (p＜0.001) and HOM $A_{IR}$ (p＜0.001) in obese group were significantly higher than those of other groups. The obesity indices correlated significantly to serum levels of insulin and leptin, but not to fasting glucose level. These results suggested that circulating leptin and insulin concentrations may act as a humoral signal indicator to adiposity-associated metabolic disorder in elementary school children.