Plasma Myostatin Increases with Age in Male Youth and Negatively Correlates with Vitamin D in Severe Pediatric Obesity.

Obesity already causes non-communicable diseases during childhood, but the mechanisms of disease development are insufficiently understood. Myokines such as myostatin and irisin are muscle-derived factors possibly involved in obesity-associated diseases. This explorative study aims to investigate whether myostatin and irisin are associated with metabolic parameters, including the vitamin D status in pediatric patients with severe obesity. Clinical, anthropometric and laboratory data from 108 patients with severe obesity (>97th percentile) aged between 9 and 19 years were assessed. Myostatin, its antagonist follistatin, and irisin, were measured from plasma by ELISA. Myostatin concentrations, particularly in males, positively correlated with age and pubertal stage, as well as metabolic parameters such as insulin resistance. Irisin concentrations correlated positively with HDL and negatively with LDL cholesterol values. For follistatin, the associations with age and pubertal stage were inverse. Strikingly, a negative correlation of myostatin with serum vitamin D levels was observed that remained significant after adjusting for age and pubertal stage. In conclusion, there is an independent association of low vitamin D and elevated myostatin levels. Further research may focus on investigating means to prevent increased myostatin levels in interventional studies, which might open several venues to putative options to treat and prevent obesity-associated diseases.

A Selective Screening Strategy Performed in Pre-School Children and Siblings to Detect Familial Hypercholesterolemia.

(1) Background: Familial hypercholesterolemia (FH), a most common genetic disorder, is underdiagnosed and untreated, especially in children. Individuals with heterozygous familial hypercholesterolemia mostly present without clinical symptoms and are not informed about their high risk for myocardial infarction. Early diagnosis and treatment can prevent premature atherosclerosis and cardiovascular events in patients with FH. The aim was to evaluate the detection rate of pre-school children with FH at school doctor visits in Vienna and, moreover, to examine the frequency of FH identified in the children's siblings by this type of screening. (2) Methods: The selective FH- screening was implemented at the school enrolment examinations in the public primary schools of Vienna. The study period included the school years starting in 2017 to 2020. FH was suspected if a questionnaire on hypercholesterolemia, or cardiovascular events in the family history or on the presence of xanthomas or xanthelasma, was positive. Subsequently, lipid testing was performed on pre-school children and their siblings and elevated lipid screening was defined as either positive by LDL-C ≥ 160 mg/dL and/or non-HDL-C ≥ 190 mg/dL or as borderline by LDL-C ≥ 130 mg/dL and/or non-HDL-C ≥ 160 mg/dL. (3) Results: 66,108 pre-school children participated in the school enrolment examination in 868 public elementary schools in Vienna. In 512 (4%) children, the questionnaire caused suspicion of FH. 344 families agreed their participation in the study. Out of 344 (52% male) tested pre-school children, 20 individuals (40% male) had elevated blood lipid levels with a mean LDL-C of 155 ± 29 mg/dL and a non-HDL-C of 180 ± 24 mg/dL. Out of 291 (44% male) tested siblings, 17 individuals (41% male) showed elevated lipids with a mean LDL-C of 144 ± 19 mg/dL, and a non-HDL-C of 174 ± 19 mg/dL. (4) Conclusions: Screening is the key for early diagnosis and treatment of FH. We have implemented a pre-school screening strategy in cooperation with school physicians. We could identify 20 pre-school children and 17 siblings with an elevated lipid screening test. Full implementation of FH-screening in the pre-school examination visits in Vienna would help to detect high-risk children.

Tryptophan Metabolism Is Associated with BMI and Adipose Tissue Mass and Linked to Metabolic Disease in Pediatric Obesity.

The obesity epidemic has contributed to an escalating prevalence of metabolic diseases in children. Overnutrition leads to increased tryptophan uptake and availability. An association between the induction of the tryptophan catabolic pathway via indoleamine 2,3-dioxygenase (IDO) activity and obesity-related inflammation has been observed. This study aimed to investigate the impact of pediatric obesity on tryptophan metabolism and the potential relationship with metabolic disease. In this prospective cohort study, plasma kynurenine, tryptophan, and serotonin levels were measured by ELISA, and IDO activity was estimated by calculating the kynurenine/tryptophan ratio in a clinically characterized population with severe obesity (BMI ≥ 97th percentile) aged 9 to 19 (n = 125). IDO activity and its product kynurenine correlated with BMI z-score and body fat mass, whereas concentrations of serotonin, the alternative tryptophan metabolite, negatively correlated with these measures of adiposity. Kynurenine and tryptophan, but not serotonin levels, were associated with disturbed glucose metabolism. Tryptophan concentrations negatively correlated with adiponectin and were significantly higher in prediabetes and metabolically unhealthy obesity. In conclusion, BMI and body fat mass were associated with increased tryptophan catabolism via the kynurenine pathway and decreased serotonin production in children and adolescents with severe obesity. The resulting elevated kynurenine levels may contribute to metabolic disease in obesity.