Kathrin Scheuermann

Serum irisin levels are regulated by acute strenuous exercise.

RATIONALE The newly discovered myokine irisin has been proposed to affect obesity and metabolism by promoting browning of white adipose tissue. However, clinical and functional studies on the association of irisin with obesity, muscle mass, and metabolic status remain controversial. Here we assessed the effect of 4 distinct exercise regimens on serum irisin levels in children and young adults and systematically evaluated the influence of diurnal rhythm, anthropometric and metabolic parameters, and exercise on irisin. RESULTS Serum irisin levels did not show diurnal variations, nor were they affected by meal intake or defined glucose load during oral glucose tolerance testing. Irisin levels decreased with age. In adults, irisin levels were higher in men than in women, and obese subjects had significantly higher levels than lean control subjects. Irisin levels were closely correlated with muscle-associated bioimpedance parameters such as fat-free mass and body cell mass. Of the 4 exercise regimens that differed in duration and intensity, we identified a clear and immediate increase in serum irisin levels after acute strenuous exercise (cycling ergometry) and a 30-minute bout of intensive exercise in children and young adults, whereas longer (6 weeks) or chronic (1 year) increases in physical activity did not affect irisin levels. SUMMARY We show that irisin levels are affected by age, sex, obesity, and particularly muscle mass, whereas diurnal rhythm and meals do not contribute to the variation in irisin levels. Short bouts of intensive exercise but not long-term elevations in physical activity, acutely and transiently increase serum irisin levels in children and adults.

Dietary Intake, FTO genetic variants, and adiposity: A combined analysis of over 16,000 children and adolescents

The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1–18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake (effect per allele = 14.3 kcal/day [95% CI 5.9, 22.7 kcal/day], P = 6.5 × 10−4), but not with protein, carbohydrate, or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele = 0.08 SD [0.03, 0.12 SD], P for interaction = 7.2 × 10−4): the association between FTO genotype and BMI was much stronger in individuals with high protein intake (effect per allele = 0.10 SD [0.07, 0.13 SD], P = 8.2 × 10−10) than in those with low intake (effect per allele = 0.04 SD [0.01, 0.07 SD], P = 0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake, and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents.

Nocturnal levels of chemerin and progranulin in adolescents: influence of sex, body mass index, glucose metabolism and sleep.

Abstract Background: Adipokines have been implicated in obesity, insulin resistance and sleep regulation. However, the role of chemerin and progranulin, two recently described adipokines, in the context of sleep remains unclear. The aim of this study was to compare nocturnal serum chemerin and progranulin levels between overweight/obese and normal-weight adolescents and to assess variations by sex, across different sleep stages and in relation to glucose metabolism. Methods: The study sample included 34 overweight/obese and 32 normal-weight adolescents from secondary schools and the Leipzig Research Center for Civilization Diseases (LIFE) Child study cohort. We obtained longitudinal serum adipokine levels during in-laboratory polysomnography followed by an oral glucose tolerance test. Results: Overweight/obese adolescents had significantly higher mean nocturnal serum chemerin area under the curve (AUC) levels (348.2±133.3 vs. 241.7±67.7 vs. ng/mL×h, p<0.001) compared to normal-weight controls. In detail, higher chemerin AUC levels in obese/overweight subjects were exclusively due to increased levels in females. No overall difference for serum progranulin AUC was found between the groups. However, when assessing sex-specific levels, serum progranulin AUC levels were ~30% higher in overweight/obese males compared to overweight/obese females. Of note, nocturnal serum chemerin and progranulin AUC did not exhibit a correlation with markers of glucose metabolism or sleep stages. Conclusions: Collectively, we report a sexual dimorphism in nocturnal progranulin and chemerin levels, which may help explain underlying differences in energy balance and body composition between males and females in the context of obesity.

Insulin-Like Peptide 5 Interacts with Sex Hormones and Metabolic Parameters in a Gender and Adiposity Dependent Manner in Humans

Insulin-like peptide 5 (INSL5) is a gut hormone produced by L-cells in the colorectal epithelium and may play a role in the regulation of metabolic processes. The biological role of INSL5 is poorly investigated and nothing is known about the role of this hormone in obese and lean humans. Two cohorts were analyzed in the study. In the first cohort (n=76) the relationship between serum levels of INSL5 and different metabolic and hormonal parameters in obese and lean men and women were investigated. In the second cohort 14 male subjects underwent bariatric surgery. Circulating levels of INSL5 were then measured before and after interventions.We report for the first time that circulating INSL5 interacts with multiple metabolic and hormonal variables in lean and obese men and women and is affected by bariatric surgery. Serum levels of INSL5 negatively correlated with testosterone and blood lipids but positively with cortisol in obese men. In contrast to males, obese women had a strong negative correlation of plasma levels of INSL5 with C-reactive protein (CRP). We observed that adipose tissue loss after bariatric surgery significantly reduced serum levels of INSL5 in obese men with and without Type 2 Diabetes Mellitus (T2DM) that was associated with the restoration of circulating levels of testosterone. All together, our data demonstrated that INSL5 may interact with some metabolic parameters in obese humans and this process is dependent of gender and obesity state.

NAMPT serum levels are selectively elevated in acute infectious disease and in acute relapse of chronic inflammatory diseases in children

Nicotinamide phosphoribosyl transferase (NAMPT) is an inflammatory adipocytokine shown to interact in immune modulation in chronic inflammatory diseases, acute respiratory distress syndrome, sepsis, cancer and obesity in adulthood. It is, however, not clear whether this association reflects a chronic elevation or acute inflammatory response. We analyzed NAMPT concentrations in distinct states of inflammation in 102 children and found consistently significantly increased NAMPT levels in subjects with acute infections. NAMPT concentrations in children with stable chronic inflammatory diseases were not significantly different, whereas in patients with acute relapse of chronic disease NAMPT was significantly higher than in children in remission or healthy controls. In states of low-grade inflammation (children with atopic disease or obesity) we did not detect alterations in NAMPT serum levels. NAMPT correlated positively with inflammatory markers such as CRP. The most predictive factor for NAMPT serum concentrations was leucocyte count and therein the neutrophil count. Furthermore, systemic circulating NAMPT levels were closely associated with NAMPT release from corresponding cultured PBMCs. In conclusion, NAMPT is selectively increased in states of acute but not chronic inflammation in children. The close relationship between systemic circulating NAMPT with leucocyte counts and release indicate that leucocytes most probably are the source of inflammation related NAMPT levels.

Impact of Weight Reduction During Adolescence on Parameters of Cardiac Geometry and Function in Obese Children

Childhood obesity is associated with changes in myocardial geometry and function indicating early onset of unfavorable alterations of the myocardium [(1,2)][1]. The value of those studies is limited by a cross-sectional study design. We aimed to assess the impact of weight reduction on temporal

Concordance of bioactive vs. total immunoreactive serum leptin levels in children with severe early onset obesity

Context Leptin secreted from adipose tissue signals peripheral energy status to the brain. Monogenic leptin deficiency results in severe early onset obesity with hyperphagia. Recently, a similar phenotype of inactivating leptin mutations but with preserved immunoreactivity and hence normal circulating immunoreactive leptin has been reported. Objective We aimed to evaluate the proportion of bioactive leptin serum levels (compared to immunoreactive leptin) as a biomarker for the screening of leptin gene mutations causing monogenic obesity. Furthermore, we aimed to compare the immunoreactive and bioactive leptin levels associations with parameters of insulin resistance and insulin secretion in obese children and adolescents. Patients and methods We measured bioactive and immunoreactive leptin levels by enzyme-linked immunosorbent assays in fasting serum samples of 70 children with severe (BMI SDS >3) non-syndromic obesity with onset <3 years of life from our Leipzig childhood obesity cohort (n = 1204). Sanger sequencing of the leptin gene was performed in probands with proportion of bioactive/immunoreactive leptin <90%. Results The mean levels of bioactive and immunoreactive leptin were almost identical (41.1±25.2 vs. 41.1±25.4ng/mL). In three probands with the lowest bioactive leptin proportion (<90%) we did not identify mutations in the leptin gene. Compared to immunoreactive leptin, bioactive leptin showed similar and slightly better statistical associations with indices of insulin resistance in correlation and multivariate analyses. Conclusion In our sample selected for severe early onset childhood obesity, we did not identify leptin gene mutations leading to decreased proportion of bioactive leptin. Nevertheless, the bioactive leptin levels were stronger associated with selected insulin secretion/resistance indices than the immunoreactive leptin levels.