Role of leptin in legg–calvé–perthes disease

Obesity is considered a clinical risk sign for Legg–Calvé–Perthes disease (LCPD). Leptin is primarily secreted by adipocytes, and it regulates adipose tissue mass and body weight. Furthermore, obesity is clearly associated with increased leptin levels. We investigated the roles of leptin and the soluble leptin receptor (sOB‐R) in LCPD. This matched case–control study included 38 male and 3 female patients with LCPD, and an equal number of age—(range was 4–12) and sex‐matched control patients with healthy fractures. Serum leptin and sOB‐R levels were quantified with ELISA. The free leptin index (FLI) was defined as the ratio of leptin to sOB‐R levels. Serum leptin levels, sOB‐R, and FLI were compared between groups. The relationship between leptin, disease severity, and treatment outcomes were analyzed in the LCPD group. There were no significant differences between groups in terms of age, sex, and body mass index (BMI) percentile. Mean leptin levels (p = 0.042), sOB‐R levels (p = 0.003), and FLI (p = 0.013) differed significantly between groups. In the LCPD group, the serum leptin levels, sOB‐R levels, and FLI differed significantly between the lateral pillar and Stulberg classification groups (p < 0.05). Also, the leptin levels and FLI increased significantly according to the lateral pillar and Stulberg classifications even after adjusting for age and BMI percentile (p < 0.05). Circulating leptin and FLI were significantly higher in the LCPD group. Furthermore, leptin, disease severity, and treatment outcomes were associated. This correlation suggests that leptin might play an important role in LCPD pathogenesis. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1605‐1610, 2013     

Obese rats with deficient leptin signaling exhibit heightened sensitivity to olfactory food cues

The Zucker rat is used as a model of genetic obesity, and while Zucker rats have been well studied for their reduced sensitivity to leptin signaling and subsequent weight gain, little work has examined their responses to environmental signals that are associated with “hedonic” feeding. This study evaluated the effects of a high‐fat food olfactory cue (bacon) in stimulating nose‐poke food‐seeking behavior on first exposure (novel) and after a period of access for consumption (familiar) in lean and obese Zucker rats at either 4 or 12 months of age, and under ad‐lib fed (unrestricted; U) or chronically food‐restricted (70% of ad‐lib; R) conditions. Baseline nose‐poke levels were comparable amongst all groups. At 4 months of age, only ObU rats displayed increased behavioral activation to familiar food cues. Twelve‐month‐old Ob rats, regardless of diet, exhibited substantially greater food‐seeking behavior when exposed to both the novel and familiar olfactory cues. A strong positive correlation between body weight and nose‐poke entries for the familiar food cue was observed at both ages, while this correlation for the novel food cue was significant in 12–month‐old rats only. Similarly, there were strong positive correlations between food intake and poke entries for the familiar food cue was observed at both ages, while this correlation for the novel food cue was significant in 12–month‐old rats only. Although it is possible that differences in olfactory sensitivity contribute to these behavioral effects, our findings support the interactions between food intake, obesity, and food‐seeking behavior and are consistent with leptin inhibiting the brain's reactivity to food cues and suggest that the enhanced sensitivity to the food cues with leptin deficiency is likely to contribute to overeating and weight gain. Synapse, 2013. © 2012 Wiley Periodicals, Inc.     

Follicular fluid levels of anti-Müllerian hormone,insulin-like growth factor 1 and leptin in women with fertility disorders

Anti-Müllerian hormone (AMH), insulin-like growth factor 1 (IGF1) and leptin are produced in the granulosa cells of follicles and play an important role in the growth and maturation of follicles. The aim of our study was to monitor AMH, IGF1 and leptin levels in a group of healthy women and compare them to a group of women with fertility disorders. The second aim was the evaluation of biomarker levels in relation to the identified cause of infertility. Totally, 146 females were enrolled into our study. Seventy-two healthy controls and seventy-four females with fertility disorders were divided into four subgroups: anovulation, endometriosis, fallopian tube damage, unknown reason. IGF1 was the only biomarker with significantly lower levels throughout the entire group with fertility disorders. We did not identify any statistically significant differences for AMH and leptin. Regarding subgroups, significant differences were only observed in the group of anovulatory women. AMH and leptin showed higher levels while IGF1 showed lower levels. In conclusion, levels of AMH, IGF1 and leptin found in follicular fluid are sensitive markers for anovulatory fertility disorders. AMH, IGF1 and leptin levels in follicular fluid have no relation to the fertility disorders caused by endometriosis, fallopian tube damage or disorders with unknown etiology.

Abbreviations: AMH: anti-Müllerian hormone; IGF1: insulin-like growth factor 1; PCOS: polycystic ovary syndrome     

瘦素和皮质醇与2型糖尿病胰岛素抵抗的关系探讨

目的探讨2型糖尿病患者血清瘦素、皮质醇水平与胰岛素抵抗的关系。方法以稳态模型胰岛素抵抗指数（HOMA—IR）作为评估胰岛素抵抗程度的指标，采用放射免疫法测定瘦素与糖皮质激素水平，分别测定30例2型糖尿病患者和30例对照组患者的空腹血糖、空腹胰岛素、瘦素、皮质醇。结果2型糖尿病患者血清瘦素、糖皮质激素水平高于对照组，且呈正相关。多元逐步回归分析提示瘦素、糖皮质激素是胰岛素抵抗的独立影响因素。结论血清瘦素、皮质激素水平与胰岛素抵抗在2型糖尿病患者呈正相关，并且是2型糖尿病的独立危险因子。     

瘦素与原发性高血压的相关性研究

目的　探讨瘦素与原发性高血压的相关性。方法　原发性高血压患者 86例 ,健康对照组 87例 ,测定其空腹血清瘦素 (leptin)、血糖、胰岛素、血脂、体质量指数 (bodymassindex ,BMI) ,稳态模型评估法计算胰岛素抵抗指数(homeostasismodelassessmentinsulinresistanceindex ,HOMA IR) ,分析瘦素与高血压的关系。结果　高血压组的瘦素、HOMA IR高于对照组 ,差异有统计学意义 (P <0 .0 5 ) ,瘦素与性别、甘油三酯 (triglyceride,TG)、腰臀比 (waist hipratio,WHR)、BMI、收缩压、HOMA IR正相关 (P <0 .0 5 )。结论　瘦素与原发性高血压相关。     

不同运动量对糖尿病大鼠血清瘦素水平的影响

目的：探讨运动与体重调节密切相关的血清瘦素水平的关系，观察不同运动量对糖尿病大鼠体重、血糖、血清胰岛素和血清瘦素的影响。方法：将实验动物分成6组，分别为正常对照组、正常运动组、糖尿病组、糖尿病小运动量组、糖尿病中运动量组和糖尿病大运动量组。运动组按Ploug方法进行游泳训练。结果：正常运动组大鼠游泳8周后的血清瘦素浓度较运动前显著降低。运动前4组糖尿病组大鼠与正常对照组相比，体重、血清胰岛素和血清瘦素水平显著降低．血糖浓度显著升高。8周后只有糖尿病中运动量组大鼠的每周体重增加数明显回升．血糖浓度较运动前降低35％，血清胰岛素浓度较运动前升高38％，血清瘦素浓度较运动前升高40％。而糖尿病小运动量组和糖尿病大运动量组大鼠运动8周后的上述指标较运动前均无显著性差异。多元相关回归分析．仅提示糖尿病大鼠血清胰岛素是血清瘦素有意义的影响因素。结论：正常生理状态下运动降低血清瘦素水平是机体为维持自身体重稳定和能量平衡的一种适应性反应；而在链脲佐菌素糖尿病状态下，瘦素似乎与胰岛素关系更密切，中等强度运动在降低血糖、改善机体对胰岛素敏感性的同时，似乎也改善了对瘦素的敏感性；运动量不足或运动量过大对糖尿病均无明显治疗效果。     

Protective Effect of Gymnema sylvestre Ethanol Extract on High Fat Diet-induced Obese Diabetic Wistar Rats

Obesity is associated with numerous co-morbidities such as cardiovascular diseases, type 2 diabetes, hypertension and others. Therefore, the present study was planned to investigate the effect of water- soluble fraction of Gymnema sylvestre ethanol extract on biochemical and molecular alterations in obese diabetic rats. Diabetes was induced by single i.v. injection of streptozotocin (45 mg/kg) via tail vein. Obesity was induced by oral feeding of high fat diet for a period of 28 days in diabetic rats. Body weight gain, food intake, water intake, hemodynamic parameters (systolic, diastolic, mean arterial blood pressures and heart rate), serum biochemical parameters (leptin, insulin, lipid levels, apolipoprotein B and glucose), cardiomyocyte apoptosis (cardiac caspase-3, Na⁺/K⁺ ATPase activity and DNA fragmentation) organs and visceral fat pad weight and oxidative stress parameters were measured. Oral treatment with water soluble fraction of Gymnema sylvestre ethanol extracts (120 mg/kg/p.o.) for a period of 21 days, resulted in significant reduction in heart rate, mean arterial pressure, serum leptin, insulin, apolipoprotein B, lipids, glucose, cardiac caspase-3 levels, Na⁺/K⁺ ATPase activity and DNA laddering, visceral fat pad and organ''s weight and improved the antioxidant enzymes levels in the high fat diet induced obesity in diabetic rats. The results of present study reveal that water soluble fraction of Gymnema sylvestre ethanol extract could be useful intervention in the treatment of obesity and type-2 diabetes mellitus.     

Genetic studies of neuropeptide Y and neuropeptide Y receptors Y1 and Y5 regions in morbid obesity

Summary Synthesis and release of neuropeptide Y (NPY) are both regulated by leptin binding to its hypothalamic receptor mediating some of the effects of leptin on food intake. Moreover, NPY administration is a powerful stimulant of feeding behaviour. Thus, we investigated the potential implication of NPY, NPY-Y1 and -Y5 subtype receptors [rNPY-Y1/-Y5] in the development of human obesity. Two complementary genetic approaches were used: 1) linkage analyses between obesity and polymorphic markers located nearby NPY and rNPY-Y1/-Y5 genes (respectively on chromosomes 7p15.1 and 4q[31.3–32]) in 93 French Caucasian morbidly obese families; 2) single strand conformation polymorphism (SSCP) scanning of the coding region of the NPY and rNPY-Y1 genes performed in 50 unrelated obese patients ascertained on the basis of a body mass index of 27 kg/m² or more and a family history of obesity. No evidence of linkage between morbid obesity or obesity-related quantitative traits and NPY and rNPY-Y1/Y5 regions was found in this population. Moreover, SSCP scanning revealed no mutation in the coding region of NPY and rNPY-Y1 genes among obese subjects. These results suggest that NPY and NPY-Y1/Y5 receptors are unlikely to be implicated in the development of human morbid obesity, at least in the French Caucasian population. [Diabetologia (1997) 40: 671–675] Received: 27 December 1996 and in revised form: 26 February 1997