Correlation Between Plasma Leptin and Endotelin-1 Plasma Level in Obese Hypertensive Subjects

Background: Leptin is associated with body weight (BW) regulation in adults and adolescents. Decrease in adiponec- tin in obese adults and adolescents may be associated with the development of obesity and insulin resistance. This study investigated the relationship of plasma leptin and adiponectin levels to changes in BW and body mass index (BMI) over fi ve years among adolescents in Taiwan. Methods: This was a prospective study involving school adolescents aged 12 to 15 years. Demographic data, anthropometric variables, and blood specimens were collected from 1500 adolescents at baseline. Body height, weight and body mass index (BMI) were evaluated at baseline, and after fi ve years in 580 ado- lescents. Plasma leptin and adiponectin levels were measured using radioimmune assay (RIA). Results: Baseline serum levels of leptin and adiponectin were higher in girls than in boys. Baseline plasma leptin levels correlated positively, and adiponectin levels negatively with BW and BMI at baseline and after fi ve years. Plasma leptin levels were negatively as- sociated with fi ve-year changes in BW and BMI both in normal-weight boys (β= -0.57, p < 0.01, and β= -0.25, p < 0.001, respectively) and girls (β= -0.28, p < 0.001, and β= -0.11, p < 0.001, respectively). The correlation between plasma adiponectin levels and fi ve-year change in BW and BMI in both genders was not statistically signifi cant. Conclusions: In Taiwanese adolescents, plasma leptin levels were negatively and signifi cantly associated with the changes in BW and BMI during the fi ve-year follow-up period in both genders, but adiponectin levels were not. Such fi nding suggests that plasma leptin levels may be a negative marker of body weight gain over time.

Objective To observe the levels of adiponection,leptin,blood fat and body mass index (BMI) after the probiotics intervention.Method We assessed the levels of adiponection,leptin,blood fat and BMI in 80 simple obesity children.They were divided into 2 groups.There were 20 boys and girls in each group.One group of children were given bifidobacterium,lactobacillus and streptococcus thermophilus 15 days.Results The levels of BMI and TG,TC,LDL-C of treatment group decreased.The levels of HDL-Cof treatment increased.But there were no significant difference between two groups (P ＞ 0.05).The levels of leptin (5.72 ± 0.39 vs 8.53 ±0.37) in treatment group decreased.The levels of adiponection (10.15 ±0.48 vs 8.81 ±0.37) Increased.There were significant difference between two groups (P ＜ 0.05).Conclusions Probiotics could decrease the levels of leptin and increase the levels of adiponection.Probiotics could become a new method to treat the simple obesity. Key words: Adiponection ; Leptin ; Probiotics ; Blood fat ; Simple obesity

Leptin (OB protein) is an important signal in the regulation of energy balance. Leptin levels correlate with adiposity, but also decrease acutely with caloric restriction and increase with refeeding. The brain is an established critical site of leptin function, yet little is known about leptin concentrations in the central nervous system relative to plasma levels, psychiatric diagnoses, and other endocrine parameters. Therefore, using a novel ultrasensitive leptin assay, we explored relationships of human plasma and cerebrospinal fluid (CSF) leptin levels to body mass index, smoking, posttraumatic stress disorder diagnosis, and levels of dopamine, monoamine metabolites, beta-lipotropin, glucocorticoid, and thyroid and cytokine hormones. A strong linear relation between CSF and plasma leptin levels in the am (r = 0.63; P < 0.002) and afternoon (r = 0.90; P < 0.0001) was revealed. CSF and plasma leptin concentrations decreased during a 12- to 20-h period of fasting. A strong association was found between plasma leptin and CSF dopamine levels (r = 0.74; P < 0.01) as well as between CSF leptin levels and urinary free cortisol (r = 0.73; P < 0.01). Both of these parameters covaried with leptin independently of adiposity, as estimated by body mass index. Implications for leptin transport, regulation, and its potential role in therapeutic strategies for obesity and diabetes are discussed.

P178 A polymorphism of the endothelin (ET)-1 gene has been associated with blood pressure (BP) of obese individuals in large population studies. We explored the variability of plasma ET in essential hypertensive sibpairs (n=14 pairs, 13 with two sibs, 1 with three sibs) in relationship to their body mass index (BMI). ET levels were measured on ad libitum Na intake (AL), after a 24 hr Na load (300 mEq iv +160 mEq po, HI) and after 24 hr of Na deprivation (10 mEq po + furosemide 120 mg, LO). BP was 147±3/90±2 mmHg and BMI 35.1±1.4, with 75% of patients exceeding 30 Kg/m 2 . ET was 4.4±0.3, 4.1±0.2, and 4.3±0.3 fmol/ml for AL, HI and LO, respectively, all higher than 20 controls (3.3±0.3, ps 2 =0.79, F=3.2, p

Leptin is an anorexigenic hormone well recognized by its role in mediating energy homeostasis. Recently, leptin has been associated with psychiatric disorders and interestingly, leptin treatment has shown antidepressant and anxiolytic effects. We examined the association of leptin levels and leptin (LEP) gene rs3828942 polymorphism with anxiety disorders considering sex differences. A cross-sectional population-based study, including 1067 young adults, of whom 291 presented anxiety disorders diagnosed by the Mini International Neuropsychiatric Interview (MINI 5.0). The rs3828942 polymorphism was genotyped by real-time PCR and ELISA measured leptin levels. Leptin levels were not associated with anxiety disorders after adjusting for sex and body mass index (BMI) [ß = - 0.009 (- 0.090-0.072); p = 0.832]. The distribution of rs3828942 genotypes was not associated with anxiety disorders. However, in a sex-stratified sample, the A-allele of rs3828942 polymorphism was associated with risk for GAD in women even when adjusting for confounding variables [OR = 1.87 (1.17-2.98); p = 0.008]. In a subsample of 202 individuals with GAD and control matched by sex and BMI, results suggest an interaction between genotypes and GAD diagnosis based on leptin levels only in the male group [F (1, 54) = 6.464; p = 0.0139]. Leptin is suggested to be related with the neurobiology of anxiety disorders in a sex-dependent manner since women carrying the A-allele of LEP rs3828942 present a higher risk for GAD, while leptin levels seem to be lower in men with GAD carrying A-allele. Studies on the relationship between leptin polymorphisms and levels are scarce and, therefore, further research is necessary.

Acute hyperinsulinemia reduces plasma leptin levels in insulin-sensitive Japanese men

reports of a relationship between altitude and circulating levels of leptin suggest a possible role of hypoxia in leptin regulation. However, studies on the changes in plasma leptin levels at altitude are controversial, with some showing an increase and others suggesting no change or a fall in these

Objective To systematic evaluation the antiepileptic drug valproic acid and topiramate effects on body weight and plasma leptin levels. Methods By searching the Cochrane Library, PubMed, EMBASE, CNKI, VIP Chinese Scientific Journals Database and Articles Database (from building a database to August 1, 2014), qualified RCT was chosen from those articles according to inclusion and exclusion criterias and evaluated their quality. Then the meta-analysis was performed by Rev Man 5.3. Results (1)A total of 70 documents retrieved for the evaluation, 12 of the literatures could be incorporated into the Meta-analysis, including a total of 634 participants, 9 literatures using valproate to treat epilepsy, 4 literatures used topiramate.(2)Meta-analysis: compared with other drugs, valproic acid treatment increased body mass index and leptin level in patients with epilepsy, BMI combined MD=0.88(95% CI: 0.45-1.31), leptin level in the combined MD=0.58(95% CI: 0.07-1.09); compared with other drugs, topiramate affect body mass index and leptin level in patients with epilepsy had no statical difference, BMI combined MD=-0.02 (95% CI: -0.62-0.58), leptin levels in the combined MD=-0.05(95% CI: -0.31-0.20). Conclusion Antiepileptic drug valproic acid may increase patients' BMI and serum leptin levels, yet topiramate in do not have influence in patients BMI and serum leptin levels; more basic and clinical researches are needed to explore serum leptin levels and the exact therapy mechanisms of antiepileptic drugs for clinicians to select antiepileptic drugs. Key words: Epilepsy; Valproic acid; Topiramate; BMI; Leptin

The purpose of this study was to examine the relationship of plasma leptin levels with respect to obesity, gender, age and insulin levels in the native Aymara population. The Aymara natives live at high altitudes in isolated regions in the north of Chile, and they maintain distinctive genetic and cultural characteristics. Plasma leptin and insulin levels were correlated with body mass index (BMI), sex and age in a sample of 147 adult Aymara subjects who participated in a cross-sectional study. Multivariate analysis showed significant differences in leptin levels (dependent variable: natural log of leptin) by gender (p < 0.0001), and by BMI (p < 0.001), without significant statistical interaction between gender and BMI. The effect of age achieved statistical significance in the multivariate analysis (p = 0.02). Gender, BMI and insulin are independently associated with plasma leptin levels. On the other hand, the multivariate analysis of the plasma insulin concentration (dependent variable: natural log of insulin levels) shows that insulin is strongly associated with BMI (p < 0.0001), although non-statistically significant differences of insulin levels by sex (p = 0.07) or age (p = 0.9) were detected at alpha 0.05 level. Thus, in the special ecosystem where the Aymara population live, a strong and independent association between sex, obesity and insulin levels with plasma leptin levels has been detected.

Background: Major risk factors of hypertension (HTN) including obesity, insulin resistance, renal pathology, increased sympathetic nerve activity (SNA) and vascular inflammation are associated with hyperleptinemia. Therefore hyperleptinemia may act as a mediator of blood pressure, linking body fat mass with changes in insulin action, sympathetic neuronal outflow and renal pathology. Objective: The objective of our study was to explore the relationship between hyperleptinemia and HTN in Pakistani population. Materials and Methods: It was a case control study of 6 months duration, carried out at Shifa College of Medicine and Shifa International Hospital, Islamabad. One hundred and four male subjects, 52 with HTN and 52 without HTN were included in this study. Leptin levels were measured by enzyme-linked immunosorbent assay (ELISA) technique. The relationship of leptin (LEP), body mass index (BMI), fasting blood sugar (FBS) and cholesterol levels with blood pressure were assessed. Results: Patients with HTN versus patients without HTN had a higher body mass index (28.0 ± 0.12 to 24.11 ± 0.27 kg/m 2 ), FBS (169.20 ± 7.34 to 127.50 ± 2.30 mg/dl), total cholesterol (160 ± 3.72 to 158 ± 2.71 mg/dl) and LEP (53.40 ± 5.32 to 21.65±3.50 ng/ml) levels. In univariate analysis, obesity, hyperglycemia and hyperleptinemia (with P values of 0.000, 0.001, 0.000, respectively), whereas in multivariate analysis, hyperglycemia and hyperleptinemia (with P values of 0.006 and 0.001, respectively) were risk factors for HTN. Our study also showed that hyperleptinemia is an independent risk factor for HTN. Conclusions: We observed a strong positive relationship between hyperleptinemia and hypertension, thereby indicating that increased leptin levels could be considered as a risk factor for HTN and cardiovascular disease. Further studies are needed to probe the underlying pathophysiological mechanisms responsible for hyperleptinemia in HTN.

Summary: In order to investigate the endothelin (ET) levels and their relationship to various hormones during the menstrual cycle, we measured endothelin-1, -2 and -3 (ET-1, -2 and -3), big ET-1 and big ET-3 levels in 27 normally cycling women (mean age 27 years). Simultaneous determination of luteinizing hormone-releasing hormone (LH-RH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, progesterone, 17α-hydroxyprogesterone (17-OHP), estrone, 17β-estradiol, ▵4-androstenedione, testosterone, active renin, angiotensin-II (A-II) and atrial natriuretic peptide (ANP) in blood, and LH, estrone and 17β-estradiol and pregnanediol levels in urine was made in the same 27 women. The levels of ET-2 in plasma were found to be 20% of those of ET-1. In addition, ET-1 levels were measured in the endometrium of the normal uterus. Plasma ET-1 and ET-3 levels fluctuated during the menstrual cycle, with a peak at the luteal phase, but showed only a negative relationship (p < 0.01) to each other at the menstrual phase, whereas big ET-1 and big ET-3 levels showed no significant changes. Plasma ET-1 and ET-3 levels showed no significant relationship to the big ETs. As for the relationship to other hormones, plasma ET-3 had a negative relationship (p < 0.01) to prolactin and a positive correlation (p < 0.01) with ANP during the entire menstrual cycle. Plasma ET-1 and ET-3 showed a partial positive or negative correlation to LH, FSH, prolactin and ANP levels, depending upon the cycle phase, whereas plasma ETs and big ETs were unrelated to other hormones in the blood, and LH, estrone, 17β-estradiol and pregnanediol in the urine throughout the menstrual cycle. At each menstrual stage, plasma ET-3 levels were more significantly related to LH, FSH, prolactin and ANP than ET-1, indicating a closer relationship between ET-3 and these circulating hormones during the menstrual cycle. The ET-1 level showed no significant change in the endometrium during the menstrual cycle.

Objective To evaluate the relationship between macrophage migration inhibitory factor (MIF) expression and obese-induced abolition of sevoflurane preconditioning-induced cardioprotection in mice. Methods Forty-eight male C57BL/6J mice, aged 4 weeks, were divided into 2 groups(n=24 each)using a random number table method: normal diet group (Lean group) and high-fat diet group (Obese group). Lean group were fed a normal diet (10% kcal) for 12 weeks, while Obese group were fed a high-fat diet (60% kcal) for 12 weeks.The weight of mice was measured.Blood samples were collected from the tail vein for determination of blood glucose concentrations, and plasma concentrations of total cholesterol, triglyceride, insulin and leptin.After measurement of the parameters mentioned above, Lean group and Obese group were divided into 3 subgroups (n=8 each) using a random number table method: sham operation groups (L-Sham group, O-Sham group), myocardial ischemia-reperfusion groups (L-IR group, O-IR group) and sevoflurane preconditioning groups (L-IR+ Sev group, O-IR+ Sev group). The mice were anesthetized and their hearts were immediately removed and retrogradely perfused in a Langendorff apparatus with an oxygenated K-H solution at 37 ℃.Hearts were continuously perfused with K-H solution for 115 min in L-Sham and O-Sham groups.Hearts were subjected to global ischemia for 25 min, followed by 60-min reperfusion after being retrogradely perfused with K-H solution in L-IR and O-IR groups.In L-IR+ Sev and O-IR+ Sev groups, hearts were subjected to 3 cycles of 5-min perfusion with sevoflurane-containing K-H solution(final concentration 0.6 mmol/L)and 5-min washout, and then hearts were subjected to global ischemia for 25 min, followed by 60-min reperfusion.Left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of increase or decrease in left ventricular pressure (±dp/dtmax) were recorded at the end of reperfusion.Hearts were obtained at the end of reperfusion for determination of myocardial infarct size and expression of MIF (by Western blot). Results Compared with Lean group, the weight, blood glucose, levels of plasma total cholesterol, triglyceride, insulin and leptin were significantly increased in Obese group (P 0.05). Conclusion The mechanism by which obese abolishes sevoflurane preconditioning-induced cardioprotection may be related to inducing MIF over-expression in mice. Key words: Macrophage migration-inhibitory factors; Obesity; Anesthetics, inhalation; Ischemic preconditioning; Myocardial reperfusion injury

Changes of circulating leptin levels during normal menstrual cycle: relationship to estradiol and progesterone.

Despite evidence for the role of adipocyte-derived hormones in insulin resistance, little is known about their levels in human lipodystrophic states. We examined the relationships of plasma leptin and adiponectin levels to fat distribution and insulin sensitivity in the HIV lipodystrophy syndrome. Cross-sectional study HIV primary care practices HIV-infected men with (n=13) and without (12) lipodystrophy and healthy uninfected controls (12). Plasma adiponectin and leptin levels were measured in the fasting state. Body composition was assessed by physical examination, dual-energy x-ray absorptiometry and computed tomography. Insulin sensitivity (S(I)) was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. Leptin levels were significantly higher in HIV-infected men with lipodystrophy as compared to HIV-infected controls (5.2 vs 3.0 ng/ml, P=0.01). Across the entire study population, leptin levels were positively correlated with measures of general adiposity. In the HIV-infected patients, leptin levels were negatively correlated with S(I) after adjustment for fat mass (r=-0.38, P=0.07). Adiponectin levels were significantly lower in HIV-infected men with lipodystrophy as compared to both HIV-infected and healthy controls (1.6 vs 3.4 microg/ml, P<0.05 and 1.6 vs 6.7 microg/ml, P<0.001, respectively). Adiponectin levels, after adjustment for fat mass, were correlated with measures of fat distribution. Finally, in the HIV-infected patients, adiponectin levels were significantly and positively correlated with S(I) after adjustment for fat mass (r=0.75, P < or = 0.001), and adiponectin level was also an independent determinant of S(I). Plasma leptin and adiponectin levels are altered in the HIV lipodystrophy syndrome. Adiponectin deficiency may play a role in the insulin resistance associated with HIV lipodystrophy.

Obesity is a multifactorial disorder influenced by the interaction of genetic, behavioral and environmental factors, control of appetite and energy expenditure, and the availability of high-calorie food. Adipocyte and adipose tissue dysfunctions are the primary defects in obesity and may link obesity to such disorders as increased insulin resistance, type 2 diabetes, fatty liver disease, hypertension, dyslipidemia, atherosclerosis and cancer. Bariatric procedures have been shown to be more effective in the management of morbid obesity than lifestyle interventions and pharmacotherapy. The aim of this study was to investigate if the significant and sustained weight loss after laparoscopic adjustable gastric banding (LAGB) resulted in an improvement in the metabolism of obese subjects in terms of serum biochemical parameters and phenotypic characteristics (cell size and number) of subcutaneous adipose tissue (SAT). Moreover, we investigated if miRNA based regulation of gene expression could be involved in the mechanisms underlying the weight loss. We evaluated 20 severely obese subjects before LAGB (T0, mean body mass index [BMI] 44.9 kg/m2) and after the loss of >30% excess weight (T1, mean BMI 31.5 kg/m2). We also evaluated 10 normal weight subjects. We collected SAT and serum samples from all subjects. Conventional biochemical parameters were measured by routine laboratory procedures, and leptin and adiponectin by Luminex xMAP technology. Five-micron sections were prepared from all paraffin-embedded SAT blocks. Slides were then stained with hematoxylin & eosin. Macrophagic infiltration were evaluated by CD68 immunohistochemical analysis. Levels of insulin, homeostasis model assessment-insulin resistance, triglycerides and liver markers as well as the leptin/adiponectin ratio were significantly lower at T1 vs T0 (p<0.05). The number of SAT adipocytes was greater and their size smaller at T1 than at T0 (p<0.05). Moreover, the morphological characteristics of SAT adipocytes at T1 did not differ from those of control adipocytes (p=0.89). Weight loss induced by bariatric surgery resulted in a significant reduction in the inflammation level, as measured by CD68 score. We found that 4% of miRNAs was differently expressed in T1 vs T0, of these 3% was up-expressed and 1% was down-expressed. Bioinformatic analysis of deregulated miRNAs showed several target genes which were involved in relevant pathways among which: pathways in cancer, regulation of endocytosis, MAPK signaling, TGF-beta signaling. LAGB induces an improvement in the obese metabolic status, which could result in a decreased risk of obese-associated diseases. Moreover, the normalization of adipocyte features at T1 vs T0 suggests a regression of SAT inflammation. Furthermore, our data support that the improvement of the metabolic status induced by bariatric surgery in our obese patients could be obtained also by miRNA-based regulation of gene expression.