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Background Severe early-onset obesity (SEOO) in children is a common feature of monogenic obesity. Gene defects of the leptin-melanocortin pathway can be analysed biochemically and genetically. The aim of this study was to search for children with leptin deficiency or biologically inactive leptin in a cohort of children with SEOO and to study associations between leptin parameters and anthropometric data. Methods The cohort included n = 50 children with SEOO (22 boys) who were recruited at one of four study centres (Germany: Ulm; Poland: Katowice, Szczecin, Rzeszow) between October 2015 and October 2017. Weight (kg) and height (m) were measured, Tanner stage was obtained and a fasting serum blood sample was taken. Serum levels of total leptin (LEP, ng/mL), biologically active leptin (bioLEP, ng/mL) and soluble leptin receptor (sLEPR, ng/mL) were measured. The body mass index (BMI [kg/m2]), BMI z-score (World Health Organization [WHO]), quotient of bioLEP/LEP and leptin-standard deviation score (LEP-SDS) (Tanner stage, BMI and sex-adjusted) were calculated. Results We did not find any child with leptin deficiency or biologically inactive leptin in our cohort. The serum LEP and bioLEP levels were strongly correlated with age (r = 0.50, p 0.05) as well as lower LEP-SDS than boys (−1.77 ± 2.61 vs. −1.40 ± 2.60, p > 0.05). sLEPR levels were negatively correlated with BMI values (r = −0.44; p Conclusions In this cohort with SEOO, we identified no new cases of children with leptin deficiency or bioinactive leptin. A strong negative correlation between the LEP-SDS and BMI values could be interpreted as relative leptin deficiency in children with SEOO. In case this hypothesis can be confirmed, these children would benefit from a substitution therapy with methionyl human leptin (metreleptin™).

Context and aims Functional leptin deficiency is characterized by high levels of circulating immunoreactive leptin (irLep), but a reduced bioactivity of the hormone due to defective receptor binding. As a result of the fact that affected patients can be successfully treated with metreleptin, it was aimed to develop and validate a diagnostic tool to detect functional leptin deficiency. Methods An immunoassay capable of recognizing the functionally relevant receptor-binding complex with leptin was developed (bioLep). The analytical quality of bioLep was validated and compared to a conventional assay for immune-reactive leptin (irLep). Its clinical relevance was evaluated in a cohort of lean and obese children and adults as well as in children diagnosed with functional leptin deficiency and their parents. Results In the clinical cohort, a bioLep/irLep ratio of 1.07 (range: 0.80–1.41) was observed. Serum of patients with non-functional leptin due to homozygous amino acid exchanges (D100Y or N103K) revealed high irLep but non-detectable bioLep levels. Upon treatment of these patients with metreleptin, irLep levels decreased, whereas levels of bioLep increased continuously. In patient relatives with heterozygous amino acid exchanges, a bioLep/irLep ratio of 0.52 (range: 0.48–0.55) being distinct from normal was observed. Conclusions The new bioLep assay is able to diagnose impaired leptin bioactivity in severely obese patients with a homozygous gene defect and in heterozygous carriers of such mutations. The assay serves as a diagnostic tool to monitor leptin bioactivity during treatment of these patients.

Background: Ghrelin is a 28-amino acid gut-brain peptide, mainly secreted by the gastric mucosa. Its effects are linked to energy homeostasis and particularly seem to increase hunger and food intake. In recent years, studies suggested that appetite-regulating peptides, such as ghrelin play a relevant role in alcoholism. Since data published to date on the potential role of ghrelin as state and/or trait marker in alcoholism and the association with craving are controversial, we aimed at further elucidating these aspects. Patients and Methods: One-hundred nine alcohol-dependent abstinent patients after withdrawal (27 f, 82 m), (ICD 10 F 10.25) and 45 healthy volunteers (12 f, 33 m) were included. Laboratory testing (Ghrelin RIA 90, Mediagnost Inc., Germany) was performed and several craving scales [Obsessive Compulsive Drinking Scale, Alcohol Urge Questionnaire and Visual Analogue Scale (VAS)] were applied at the beginning and at the end of the 3-week rehabilitation program. Results: (1) Ghrelin levels are significantly higher in female alcohol-dependent patients as compared to controls, not, however, in men alcoholics. (2) In several statistical subanalyses, an association of craving and ghrelin was found. The results, however, remain heterogeneous. Conclusion: The data suggest gender-dependent ghrelin levels in alcohol-dependent patients. We therefore conclude, that it might be useful to perform statistical analyses gender-specific. With regard to a potential correlation of ghrelin and craving the results seem to depend on gender, duration of the abstinence period and the instrument used.

Evidence is growing that appetite regulating peptides such as leptin and ghrelin, but also other hormones including prolactin are altered in alcoholism. The brain pro-opiomelanocortin (POMC) system which has important mediating roles in alcohol intake also has important functions in prolactin regulation and energy homeostasis. Furthermore, it has been demonstrated to be functionally integrated with leptin regulation. The satiety factor leptin seems to be counteracted by the gut-derived peptide ghrelin which increases hunger and food intake. Consequently, the POMC system may have a role in integrating regulation of alcohol effects and these seemingly disparate regulatory systems. The goal of this mini-review is to discuss the results of some recent investigations of the potential interactions of these systems with acute and chronic alcohol responses.

As, for ethical reasons, it is difficult to investigate by an experiment the effect of acute intoxication on leptin levels in alcoholics, we tested the hypothesis of lowered levels as an effect of acute ethanol intake inhealthy volunteers. The subjects comprised (1) 17 healthy male participants, recruited via newspaper advertisements [age 29 + 3.75 years, body mass index (BMI) 24.3 + 3.5, leptin at baseline 3.3 + 3.1 ng/ml]; (2) for comparison, leptin levels of 16 male alcoholic patients at day I of withdrawal were used. They were characterized as follows: (mean, median, standard deviation and range) age in years (41.1, 40.5, 10.2, 24, 57), BMI (23.3, 21.7, 5.4, 16.6, 37.5), 1032g of ethanol (median) consumed within the last 7 days, leptin levels 2.3mglml. A placebo-controlled double-blind trial teas performed. Leptin levels of blood samples were taken at baseline (t 1 ), before ethanol intake (t 2 ), when blood alcohol had reached its maximum (t 3 ) and the morning after (t 4 ). The oral dose of ethanol administered was 0.6 g/kg ethanol. (1) Volunteers: (a) the ethanol and placebo group exhibited leptin levels corresponding closely with levels measured at baseline (t 1 ) (rs = 0.85, p < 0.0001) and follow-up (t 4 ) (r s = 0.768, p < 0.0001). (b) Leptin levels for the placebo and the alcohol-consuming (verum) group did not differ significantly at baseline, after ethanol intake or on the morning after [Mann - Whitney U-test (p = 0.669, p = 1.0 and p = 0.887, respectively)]. (2) Leptin levels in relation to BMI did not significantly differ at any measurement time in either group. (3) Leptin levels/BMI of the healthy volunteers at t 1 and t 4 were not significantly different from those of 16 alcoholics. The data do not support the hypothesis of a significant effect of acute moderate alcohol intake on leptin levels in healthy volunteers.

Background: Multiple sclerosis (MS) is a frequent and often severe autoimmune disease of the central nervous system. We describe a newly developed enzyme-linked immunosorbent assay (ELISA)-based test system for the assessment of neuronal autoantibodies in serum and cerebrospinal fluid (CSF). This tool could help define autoimmune status and thus be a potential means of therapeutic surveillance. Methods: We used an assay system (ELISA, E100, Mediagnost) based on purified bovine antigens [myelin-oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), myelin-associated glycoprotein (MAG), proteolipid protein (PLP) and alpha-B-crystalline (CRY)] antibodies for the measurement of specific immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies. Assay characteristics and preliminary validation were conducted by measurement of serum and CSF samples from 41 MS patients and 128 patients with other neurological diseases (OND). Results: We measured the inter- (17.8/10.1%) and intra-assay variability (5.5/6.7%); linearity (1:250– 1:16,000), and specificity of IgG and IgM. We demonstrate that by the results of this test system MS patients can be differentiated from patients with OND. Conclusions: The ELISA kit we evaluated is suitable for the measurement of neuronal autoantibodies. The initial validation demonstrates its potential use in the differential diagnosis of central neuronal system diseases. Clin Chem Lab Med 2009;47:1395–400.