• Journal of Yeungnam Medical Science
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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.

• Clinical and Experimental Pediatrics
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• v.51 no.3
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• pp.256-261
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• 2008

Purpose : Leptin and adiponectin are two representative adipocytokines. Leptin increases, but adiponectin decreases, with obesity and insulin resistance. We aimed to study the relationship between the leptin/adiponectin ratio and insulin resistance in healthy children. Methods : Seventy-seven healthy children (36 boys and 41 girls) were enrolled in this study. Anthropometric measurements were performed, and the percentage of weight for height (%WFH) was calculated in each subject. Fasting plasma levels of glucose, insulin, leptin, adiponectin, testosterone, estradiol, and sex-hormone binding globulin (SHBG) were measured. The free androgen index (FAI) was used as a representative of testosterone bioactivity. The homeostasis model assessment was used to estimate the degree of insulin resistance (HOMA-IR). Results : In the boys, HOMA-IR was significantly correlated with age, pubertal stage, free androgen index (FAI), leptin, and the leptin/adiponectin ratio. HOMA-IR was also significantly related to age, percentage of weight for height (%WFH), pubertal stage, estradiol, leptin, and the leptin/adiponectin ratio in girls. The leptin/adiponectin ratio was independently related to HOMA-IR after adjusting for age, %WFH, and FAI in the boys (P<0.05). The leptin/adiponectin ratio was not independently related to HOMA-IR after adjusting for age, %WFH, and estradiol in girls. Conclusion : In non-obese healthy children, the leptin/adiponectin ratio was significantly correlated with insulin resistance. The leptin/adiponectin ratio was independently related to insulin resistance even after adjusting for age, degree of obesity, and androgen levels in healthy boys.

• 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.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.2
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• pp.163-173
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• 2020

Purpose: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children. Methods: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5-9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI. Results: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak. Conclusion: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.

• Molecules and Cells
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• v.41 no.3
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• pp.244-255
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• 2018

Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesity-associated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + ${\alpha}$-bungaratoxin (${\alpha}-BGT$) group (As IV+${\alpha}-BGT$ group). As IV ($20mg{\cdot}Kg^{-1}{\cdot}d^{-1}$) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of ${\alpha}7nAChR$, inhibitor of nuclear factor ${\kappa}B$ kinase subunit ${\beta}/nuclear$ factor ${\kappa}B$ ($IKK{\beta}/NF-KB$) and pro-inflammatory cytokines ($IL-1{\beta}$ and $TNF-{\alpha}$) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of ${\alpha}7nAChR$. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated ${\alpha}7nAchR$ and suppressed $IKK{\beta}/NF-KB$ signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of ${\alpha}7nAChR$ selective antagonist ${\alpha}-BGT$ could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesityassociated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased ${\alpha}7nAchR$ expression.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.125-130
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• 2005

We examined the effect of leptin on the insulin resistance in skeletal muscles by measuring the glucose transport. Male Wistar rats were fed with chow or high-fat diets for 30 days. Three days before sacrifice, high-fat fed rats were subcutaneously injected with leptin (1 mg/kg body weight) for 3 days. The glucose transports in the epitrochlearis and soleus muscle were not different among the experimental groups under basal state, however these were decreased significantly in the high fat-diet rats under insulin-stimulation (p＜0.01). Leptin treatment recovered the decreased glucose transport in the epitrochlearis (p＜0.05) and soleus (p=0.08). Triglyceride concentration in the soleus muscle was increased significantly in the high fat-fed rats, compared to chow diet rats (p＜0.01), and it was decreased significantly by leptin treatment (p＜0.01). The glucose transport was measured under basal and $60{\mu}u/ml$ of insulin with or without 50 ng/ml of leptin. Leptin had no direct stimulatory effect on glucose transport under both basal and insulin-stimulated conditions in vitro. These results demonstrate that leptin injection to high fat diet fed rats recovered impaired insulin responsiveness of the skeletal muscles and muscle triglyceride concentration. However, there was no direct stimulatory effect of leptin on insulin sensitivity of the skeletal muscle in vitro.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.11-21
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• 2021

Adipose tissue secretes many adipokines which contribute to various metabolic processes, such as blood pressure, glucose homeostasis, inflammation and angiogenesis. The biology of adipose tissue in an obese individual is abnormally altered in a manner that increases the body's vulnerability to immune diseases, such as psoriasis. Psoriasis is considered a chronic inflammatory skin disease which is closely associated with being overweight and obese. Additionally, secretion of leptin, a type of adipokine, increases dependently on adipose cell size and adipose accumulation. Likewise, high leptin levels also aggravate obesity via development of leptin resistance, suggesting that leptin and obesity are closely related. Leptin induction in psoriatic patients is mainly driven by the interleukin (IL)-23/helper T (Th) 17 axis pathway. Furthermore, leptin can have an effect on various types of immune cells such as T cells and dendritic cells. Here, we discuss the relationship between obesity and leptin expression as well as the linkage between effect of leptin on immune cells and psoriasis progression.

• Clinical and Experimental Pediatrics
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• v.48 no.10
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• pp.1076-1081
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• 2005

Purpose : Insulin resistance is the most important risk factor linked to the development of impaired glucose tolerance(IGT), diabetes mellitus and cardiovascular diseases in childhood and adolescent obesity, The purpose of this study was to see whether insulin resistance of obese adolescent is higher than that of obese children. and to analyze gender difference and affecting factors of insulin resistance. Methods : Of the 9,837 school children from 5 to 16 tears old, 92 obese children and 187 adolescent, underwent a two-hour oral glucose tolerance test and plasma glucose, insulin, lipid profiles, leptin and high sensitive C-reactive protein(hs-CRP) were measure. Results : Plasma insulin levels of female were higher compared to those of males during oral glucose tolerance test(P<0.05). Four(4.3%) in obese children and twenty five(13.3%) in obese adolescents met the criteria of IGT. Female, leptin, adiponectin and triglyceride concentrations were strongly correlated with homeostatic model assessment insulin-resistance(HOMA-IR) by multiple linear regression analysis(P<0.05). Conclusion : Obese adolescents might have higher insulin concentrations compared to obese children and obese girls higher insulin concentrations than obese boys. Obese boys and children with impaired glucose tolerance have higher insulin concentrations than those with normal glucose tolerance. HOMA-IR was significantly correlated with female, plasma leptin, adiponectin and triglyceride concentrations.

• Journal of Digital Convergence
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• v.13 no.4
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• pp.387-393
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• 2015

The purpose of this study is investigating the effects of combination of policosanol intake and combined exercise to the defence mechanism and the changes of fat cell control hormones by analyzing the changes of inflammatory markers LDH and CPK, and Leptin when having policosanol intake and combined exercise together against obese women for 12 week. These groups are randomly assigned to the control group, policosanol intake group, combined exercise group and combined treatment group with 12 obese women in esch group and they performed muscular resistance exercise and an aerobic exercise which was walking twice a week. After 12 weeks the LDH showed significant differences(p<.01) at exercise period, and also showed the significant differences(p<.05) in the effect of the interaction between exercise period and group. The changes in Leptin showed significant differences(p<.001) at exercise period. In summary, carrying out together of the aerobic exercise, muscular resistance exercise or policosanol intake can be considered to have the beneficial effects to prevent various disease which caused by inflammatory maker and Leptin and it also increases its effects.