• Journal of Yeungnam Medical Science
• /
• 제30권1호
• /
• pp.4-9
• /
• 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
• /
• 제51권3호
• /
• pp.256-261
• /
• 2008

목 적 : 렙틴과 아디포넥틴은 대표적인 adipocytokine으로 비만도 및 인슐린 저항성이 증가함에 따라 혈중 렙틴은 증가하고 아디포넥틴은 감소하는 것으로 알려져 있다. 본 연구에서는 건강한 소아에서 렙틴/아디포넥틴 비와 인슐린 저항성 사이에 어떠한 연관성이 있는지 알아보고자 하였다. 방 법 : 7-15세의 건강한 소아 77명(남아 36명, 여아 41명)을 대상으로 하여 신체계측을 하고 공복 후 채혈하여 혈당, 인슐린, 렙틴, 아디포넥틴, 총 테스토스테론, 에스트라디올 및 SHBG를 측정하였다. 활성 남성호르몬 농도로는 FAI를, 인슐린 저항성의 척도로는 HOMA-IR을 사용하였다. 결 과 : 남아에서 HOMA-IR은 연령, 사춘기 단계, FAI, 렙틴 및 렙틴/아디포넥틴 비와 의미있는 양의 상관관계를 보였다. 여아에서는 HOMA-IR과 연령, %WFH, 사춘기 단계, 에스트라디올, 렙틴, 그리고 렙틴/아디포넥틴 비 사이에 의미있는 양의 상관성이 관찰되었다. 다중회귀분석 결과, 남아에서 렙틴/아디포넥틴 비는 연령, %WFH, 및 FAI로 보정한 후에도 HOMA-IR과 독립적인 연관성을 보였다(P=0.010). 여아에서는 렙틴/아디포넥틴 비와 HOMA-IR 사이에 독립적인 연관성을 보이지 못하였다. 결 론 : 비만하지 않은 건강한 소아에서도 렙틴/아디포넥틴 비는 인슐린 저항성과 의미있는 연관성을 보였으며, 남아에서는 연령, 비만도 및 남성호르몬 농도로 보정한 후에도 렙틴/아디포넥틴 비와 인슐린 저항성 사이에 독립적인 연관성이 있었다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제10권1호
• /
• pp.1-6
• /
• 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
• /
• 제23권2호
• /
• pp.163-173
• /
• 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
• /
• 제41권3호
• /
• pp.244-255
• /
• 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
• /
• 제35권7호
• /
• pp.737-742
• /
• 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
• /
• 제9권2호
• /
• pp.125-130
• /
• 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
• /
• 제29권1호
• /
• pp.11-21
• /
• 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
• /
• 제48권10호
• /
• pp.1076-1081
• /
• 2005

목 적 : 인슐린 저항성은 소아 및 청소년 비만증에서 내당능 장애, 당뇨병증, 심혈관계질환을 일으키는 중요한 위험요인 중 하나로 알려져 있다. 따라서 이 연구의 목적은 비만증 청소년이 소아에 비해 인슐린저항성이 증가하는가 그리고 성별에 따른 차이점을 규명하며 인슐린저항성에 영향을 미치는 요인들을 분석하고자 한다. 방 법 : 5-16세의 학생 9,837명을 신체검사하여 92명의 비만증 소아와 187명의 비만증 청소년을 선별하였고, 이들을 대상으로 당부하검사, 공복상태의 혈당, 인슐린농도, 총콜레스테롤, LDL-콜레스테롤, HDL-콜레스테롤, 중성지방의 농도, leptin, hs-CRP 및 adiponectin 농도를 측정하였다. 결 과 : 당부하검사를 통한 비만증 소아 및 청소년에서 성별에 따른 인슐린의 농도는 여자에서 인슐린의 농도가 높았다(P<0.05). 비만증 소아에서 4명(4.3%), 비만증 청소년에서 25명(13.3%)에서 내당능 장애로 나타났으며, 당뇨병으로 진단된 경우는 1례도 없었다. 인슐린 저항성은 여자, leptin, adiponectin, 중성지방의 농도와 밀접한 상관관계가 있었다(P<0.05). 결 론 : 비만증에서 인슐린 저항성은 소아보다 청소년에서 컸으며, 남자보다 여자에서 컸다. 또한 leptin 및 중성지방의 농도가 높을수록, adiponectin의 농도가 낮을수록 인슐린 저항성이 컸다. 소아 및 청소년 비만증에서 인슐린 저항성에 미치는 요인들에 관하여 좀 더 많은 연구가 필요하다.

• 디지털융복합연구
• /
• 제13권4호
• /
• pp.387-393
• /
• 2015

본 연구는 12주간 비만 여성을 대상으로 규칙적인 복합운동과 policosanol 섭취 병행이 염증표지인자 LDH와 CPK, Leptin에 미치는 변화를 분석함으로써 복합운동과 policosanol 섭취 병행이 생체 방어반응과 지방세포 조절 호르몬 변화에 미치는 영향을 규명하는데 있다. 통제집단 12명, policosanol 섭취집단 12명, 복합운동집단 12명, 복합 처치 집단 12명으로 무선 배정하였고 주 2회는 근저항성 운동, 주2회는 걷기형태의 유산소운동을 실시하였다. 12주 후 LDH는 운동시기에서 유의한 차이를 보였고(p<.01), 운동시기와 그룹간의 상호작용 효과에서도 유의한 차이 (p<.05)를 나타냈다. 또한 leptin의 변화에서는 운동시기에 유의한 차이(p<.001)를 나타내었다. 이상의 결과를 종합하면 복합 운동이나, policosanol 섭취는 염증표지인자와 렙틴에 긍정적인 영향을 미치며, 복합운동과 policosanol 섭취의 병행은 그 효과를 더욱 증대시키는 것으로 사료된다.