Adipose tissue-produced hormones significantly affect the metabolism of lipids and carbohydrates as well as numerous other processes in human body. It is generally accepted that endocrine dysfunction of adipose tissue may represent one of the causal links between obesity and insulin resistance/diabetes. Epidemiological studies underlined that obesity represents a significant risk factor for the development of cancer, although the exact mechanism of this relationship remains to be determined. Multiple recent studies have indicated that some of adipose tissue-derived hormones may significantly influence the growth and proliferation of tumorous stroma and malignant cells within. Here we review current knowledge about possible relationship of leptin and adiponectin to the etiopathogenesis of different malignant tumors. Most of the studies indicated that while leptin may potentiate the growth of cancer cells in vitro, adiponectin appears to have an opposite effect. Further studies are necessary to decide whether obesity-induced endocrine dysfunction of adipose tissue can directly influence carcinogenesis in different tissues and organs.
The hormone leptin, which is thought to be primarily produced by adipose tissue, is a polypeptide that was initially characterized by its ability to regulate food intake and energy metabolism. Leptin appears to signal the status of body energy stores to the brain, resulting in the regulation of food intake and whole-body energy expenditure. Subsequently, it was recognized as a cytokine with a wide range of peripheral actions and is involved in the regulation of a number of physiological systems including reproduction. In the fed state, leptin circulates in the plasma in proportion to body adiposity in all species studied to date. However other factors such as sex, age, body mass index (BMI), sex steroids and pregnancy may also affect leptin levels in plasma. In pregnant mice and humans, the placenta is also a major site of leptin expression. Leptin circulates in biological fluids both as free protein and in a form that is bound to the soluble isoform of its receptor or other binding proteins such as one of the immunoglobulin superfamily members Siglec-6 (OBBP1). Although the actions of leptin in the control of reproductive function are thought to be exerted mainly via the hypothalamicpituitary-gonadal axis, there have also been reports of local direct effects of leptin at the peripheral level, however, these data appear contradictory. Therefore, there is a need to summarize the current status of research outcomes and analyze the possible reasons for differing results and thus provide researchers with new insight in designing experiments to investigate leptin effect on reproduction. Most importantly, our recent experimental data suggesting that reproductive performance is improved by decreasing concentrations of peripheral leptin was unexpected and cannot be explained by hypotheses drawn from the experiments of excessive exogenous leptin administration to normal animals or ob/ob mice., M. Herrid, S. K. A. Palanisamy, U. A. Ciller, R. Fan, P. Moens, N. A. Smart, J. R. McFarlane., and Obsahuje bibliografii
Obesity in childhood increases the risk of obesity in adulthood and is predictive for the development of metabolic disorders. The fatty acid composition is associated with obesity and obesityassociated disorders. We investigated the relationship between serum fatty acids composition, adiposity, lipids profile, parameters of glucose metabolism and leptin. The study subjects were 380 adolescents aged 15.0-17.9 years. The study's variables included anthropometric measurements, levels of serum lipids and hormonal parameters. Individual fatty acids were determined in plasma by gas-liquid chromatography. Palmitoleic acid (16:1n-7, PA) significantly positively correlated with percentage of body fat. Saturated fatty acids in phospholipids (PL) positively correlated with BMI and percentage of body fat. PA content in all lipids classes positively correlated with total cholesterol (TC), HDL cholesterol, triglycerides (TG) levels. Stearoyl-CoA desaturase (SCD) activity positively correlated with percentage of body fat and positive correlations of SCD and PA level with leptin were found. Plasma PA content and SCD are associated with adiposity and leptin in obese adolescents. No significant correlation between PA level and insulin resistance was found. Palmitoleate positively correlated with TC, HDL cholesterol, TG and LDL cholesterol levels., P. Hlavaty, E. Tvrzicka, B. Stankova, H. Zamrazilova, B. Sedlackova, L. Dusatkova, V. Hainer, M. Kunesova., and Obsahuje bibliografii
Physiologically, leptin concentration is controlled by circadian rhythm. However, in critically ill patients, circadian rhythm is disrupted. Thus we hypothesized that circadian leptin concentration changes are not preserved in critically ill patients. Ten consecutive critically ill heart failure patients with the clinical indication for mechanical ventilation and sedation were included into our study. Plasma leptin concentration was measured every 4 h during the first day (0-24 h) and during the third day (48-72 h) after admission. During the first day, there were significant leptin concentration changes (ANOVA, p<0.05), characterized by an increase in concentration by 44 % (16-58 %); p=0.02 around noon (10 am-2 pm) and then a decrease in concentration by 7 % (1-27 %); p=0.04 in the morning (2 am-6 am). In contrast, there was no significant change in leptin concentration during the third day after admission (ANOVA, p=0.79). Based on our preliminary results, we concluded that in critically ill heart failure patients, the circadian rhythm of plasma leptin concentration seems to be preserved during the first but not during the third day after admission., I. Cundrle Jr., P. Suk, V. Sramek, Z. Lacinova, M. Haluzik., and Obsahuje bibliografii
Increases in resting energy expenditure (REE) likely contribute to weight loss in various chronic diseases. In chronic obstructive pulmonary disease (COPD), relationships between the ventilatory impairment and increased REE, and between disturbances in adipokines and weight loss were previously described. Therefore, we investigated serum levels and adipose tissue expression of leptin and adiponectin, and their relationships to REE in patients with COPD. In 44 patients with stable COPD (38 male; age 62.3±7.2 years), REE was assessed using indirect calorimetry. Subcutaneous adipose tissue samples were analyzed using realtime PCR. From underweight [n=9; body mass index (BMI) <20.0 kg.m−2 ], to normal weight-overweight (n=24, BMI=20.0- 29.9 kg.m−2 ) and obese patients (n=11; BMI≥30 kg.m−2 ), REE adjusted for body weight decreased (32.9±6.1 vs. 26.2±5.8 vs. 23.9±6.6 kcal.kg−1 .24 h−1 , p=0.006), serum levels and adipose tissue expression of leptin increased (p<0.001 for both), and serum and adipose tissue adiponectin decreased (p<0.001; p=0.004, respectively). REE was inversely related to serum and adipose tissue leptin (R=−0.547, p<0.001; R=−0.458, p=0.002), and directly to serum adiponectin (R=0.316, p=0.039). Underweight patients had increased REE compared to normal weight-overweight patients, in association with reductions in serum and adipose tissue leptin, and increased serum adiponectin, suggesting a role of adipokines in energy imbalance in COPD-related cachexia, M. Brúsik ... [et al.]., and Obsahuje seznam literatury
The aim of this study was to investigate the concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), leptin, tumor necrosis factor-α, interleukin (IL)-1β and IL-6, in cycles with a premature rise of serum progesterone. 25 intracytoplasmic sperm injection (ICSI) cycles with (Group 1) and 25 ICSI cycles without a premature progesterone elevation (Group 2) were included. The cut-off value of serum progesterone on the day of human chorionic gonadotropin (hCG) administration was 0.9 ng/ml. The indication for ICSI was male factor infertility exclusively. On the day of hCG injection, serum IL-6, VEGF and bFGF were significantly higher in Group 1 (7.7±24.5 pg/ml, 290.2±161.4 pg/ml and 15.7±8.2 ng/ml respectively) than in Group 2 (1.7±0.7 pg/ml, 175.2±92.1 pg/ml, and 9±1.6 ng/ml respectively). On the day of follicular puncture, serum cytokine concentrations were similar in the two groups. IL-6 intrafollicular concentrations were higher in Group 1 (14.7±20.7 pg/ml) than in Group 2 (9±9.3 pg/ml, p=0.031). There were no differences regarding the ICSI outcome. Patients with serum progesterone above 0.9 ng/ml, have elevated serum concentrations of IL-6, VEGF, and bFGF, as well as elevated intrafollicular concentrations of IL-6. The outcome of ICSI cycles is not associated with premature elevation of progesterone when the cut-off value is set at 0.9 ng/ml., N. Nikolettos, B. Asimakopoulos, F. Köster, B. Schöpper, Ch. Schulz, G. S. Caglar, A. Efthimiadou, O. Pagonopoulou, K. Diedrich, S. Al-Hasani., and Obsahuje bibliografii a bibliografické odkazy
In this study, we describe changes of plasma levels of the hypothalamic neuropeptide orexin A in obese children during the reduction of body weight and its relationship to other biochemical and anthropometrical parameters. We measured orexin A fasting plasma levels by the RIA method in 58 obese children - 33 girls and 25 boys; mean age 13.1±0.38 years (range 7-18.5) before and after 5 weeks of weight-reduction therapy. Leptin, IGF-1, and IGFBP-3 levels were measured in all the subjects and were compared to orexin A levels and anthropometrical data. Average weight in subjects before weight-reduction was 74.2±2.79 kg and after weight-loss 67.4±2.60 kg (p<0.0001). Orexin A levels before the therapy were 33.3±1.97 pg/ml and after the therapy 51.7±3.07 pg/ml (p<0.0001). Levels of orexin A were not significantly different between girls and boys (p=0.7842). We found negative correlation between orexin A and age (r = -0.5395; p<0.0001), body height (r = -0.4751; p=0.0002), body weight (r = -0.4030; p=0.0017) and BMI (r = -0.2607; p=0.0481). No correlation was found between orexin A and IGF-1, IGFBP-3 or leptin. Orexin A plasma levels increased during body weight loss, whereas the reverse was true for leptin levels. These findings support the hypothesis that orexin A may be involved in regulation of nutritional status in children., J. Bronský, J. Nedvídková, H. Zamrazilová, M. Pechová, M. Chada, K. Kotaška, J. Nevoral, R. Průša., and Obsahuje bibliografii a bibliografické odkazy
Potential changes in the activity of endocrine axes related to growth as a result of leptin administration during embryonic development of birds were evaluated in the Japanese quail as a model bird with fast growth and development. On day 5 of incubation, 0.1 µg or 1 µg of recombinant mice leptin in 50 µl of phosphate buffered saline were injected into the albumen of eggs. Animals from each group were killed by decapitation on day 0, 2, 5, 7, 14, 21, 28, 35, 42, 49 and 56 of life. Plasma concentrations of triiodothyronine (T3), thyroxin (T4), corticosterone, testosterone, total lipids, triacylglycerols, cholesterol, glucose and alkaline phosphatase activity were measured. Quail treated by leptin hatched earlier (5-24 hours) and had a higher body weight than the control group (P<0.05-0.001). Mean body weight across the whole observed period was higher in both treated groups as compared to the control group (P<0.05). Leptin in ovo administration was accompanied by changes of endocrine and metabolic parameters during postembryonic development. The most prominent changes appeared immediately after hatching (T3, T4, total lipids, triacylglycerols) and before sexual maturity. It is suggested that leptin acts as a general signal of low energy status to neuroendocrine systems in birds which improves utilization of nutrients., D. Lamošová, M. Máčajová, M. Zeman, Š. Mózeš, D. Ježová., and Obsahuje bibliografii
In the present study we used the primary cultures of chick embryonic muscle and liver cells as a model for potential mutual combination effects of leptin and insulin, respectively. The influence of both hormones on the proliferation and protein synthesis was dose-dependent and related to the age of embryos from which the cells were isolated. Leptin (10 and 100 ng/well) increased the proliferation (estimated by DNA content and incorporation of labeled thymidine into DNA) and protein synthesis (determined by incorporation of labeled leucine into proteins) of muscle cells. The effect of leptin and insulin in muscle cells was similar. In younger embryo (11-day-old) the lower dose of leptin was more effective than the higher one compared to the insulin effect. Mutual effects of leptin and insulin were neither additive nor synergistic and were equivalent to the effects of individual hormones. In hepatocytes the influence of leptin was dependent on the age at which the cells were isolated (11- and 19-day-old embryos). The presence of insulin neither potentiated nor inhibited the effect of leptin., D. Lamošová, M. Zeman., and Obsahuje bibliografii
The aim of this study was to explore the changes in the adipokines leptin and adiponectin in obese patients with type 1 diabetes mellitus (T1DM) who underwent seven days of fasting and 21 days of low-calorie diet (LCD). The plasma leptin and adiponectin concentrations were measured in 14 obese patients with T1DM at baseline, immediately after 7 days of fasting, and after 21 days of LCD. 13 non-obese patients with T1DM were studied only after an overnight fasting. Bioimpedance technique was used for determination of body composition. Obese T1DM patients lost 6.0 kg (6.0; 6.8) (median, 25 %; 75 %) and decreased their fat tissue after fasting and LCD. Plasma leptin in obese T1DM was significantly higher than in non-obese T1DM patients: 9.10 (5.06; 25.89) vs. 1.71 (1.12; 7.08) μg ∙ l-1 and transiently decreased immediately after fasting: 3.45 μg ∙ l-1 (1.47; 7.00), (P<0.05). Adiponectin/leptin ratio in obese T1DM was significantly lower than in non-obese T1DM patients: 0.67 (0.57; 1.49) vs. 3.50 (2.46; 6.30) ∙ 103 and transiently increased immediately after fasting: 2.22 (1.26; 3.24) ∙ 103, (P<0.05). We conclude that obese patients with T1DM are characterized by hyperleptinemia that is reduced by prolonged fasting, but only slightly affected by low calorie diet., F. Musil, V. Blaha, A. Ticha, R. Hyspler, M. Haluzik, J. Lesna, A. Smahelova, L. Sobotka., and Obsahuje bibliografii