Longitudinal Association of Telomere Dynamics with Obesity and Metabolic Disorders in Young Children.

In adults, short leukocyte telomere length (LTL) is associated with metabolic disorders, such as obesity and diabetes mellitus type 2. These associations could stem from early life interactions between LTL and metabolic disorders. To test this hypothesis, we explored the associations between LTL and metabolic parameters as well as their evolution over time in children with or without obesity at baseline. Seventy-three (n = 73) children attending our Outpatient Clinic for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence, aged 2-10 years (mean ± SD: 7.6 ± 2.0 years), were followed for 2 to 4 years. Anthropometric, clinical, and biological (including LTL by Southern blot) measurements were performed annually. Baseline LTL correlated negatively with BMI (p = 0.02), fat percentage (p = 0.01), and blood glucose (p = 0.0007). These associations persisted after adjustments for age and sex. No associations were found between LTL attrition during the follow-up period and any of the metabolic parameters. In young children, obesity and metabolic disturbances were associated with shorter telomeres but were not associated with more pronounced LTL attrition. These results suggest that short telomeres contribute to the development of obesity and metabolic disorders very early in life, which can have a major impact on health.

The Effect of a Comprehensive Life-Style Intervention Program of Diet and Exercise on Four Bone-Derived Proteins, FGF-23, Osteopontin, NGAL and Sclerostin, in Overweight or Obese Children and Adolescents.

The adipose and bone tissues demonstrate considerable interconnected endocrine function. In the present study, we determined the concentrations of fibroblast growth factor-23 (FGF-23), osteopontin, neutrophil gelatinase-associated lipocalin (NGAL) and sclerostin in 345 children and adolescents who were overweight or obese (mean age ± SD mean: 10.36 ± 0.16 years; 172 males, 173 females; 181 prepubertal; and 164 pubertal) before and after their participation in a comprehensive life-style intervention program of diet and exercise for one year. Following the one-year life-style interventions, there was a significant decrease in BMI (p < 0.01), FGF-23 (p < 0.05), osteopontin (p < 0.01) and NGAL (p < 0.01), and an increase in sclerostin (p < 0.01) concentrations. BMI z-score (b = 0.242, p < 0.05) and fat mass (b = 0.431, p < 0.05) were the best positive predictors and waist-to-height ratio (WHtR) (b = −0.344, p < 0.05) was the best negative predictor of the change of osteopontin. NGAL concentrations correlated positively with HbA1C (b = 0.326, p < 0.05), WHtR (b = 0.439, p < 0.05) and HOMA-IR (b = 0.401, p < 0.05), while BMI (b = 0.264, p < 0.05), fat mass (b = 1.207, p < 0.05), HDL (b = 0.359, p < 0.05) and waist circumference (b = 0.263, p < 0.05) were the best positive predictors of NGAL. These results indicate that FGF-23, osteopontin, NGAL and sclerostin are associated with being overweight or obese and are altered in relation to alterations in BMI. They also indicate a crosstalk between adipose tissue and bone tissue and may play a role as potential biomarkers of glucose metabolism. Further studies are required to delineate the physiological mechanisms underlying this association in children and adolescents.

A Comprehensive, Multidisciplinary, Personalized, Lifestyle Intervention Program Is Associated with Increased Leukocyte Telomere Length in Children and Adolescents with Overweight and Obesity.

Leucocyte telomere length (LTL) is a robust marker of biological aging and is associated with obesity and cardiometabolic risk factors in childhood and adolescence. We investigated the effect of a structured, comprehensive, multidisciplinary, personalized, lifestyle intervention program of healthy diet and physical exercise on LTL in 508 children and adolescents (239 males, 269 females; 282 prepubertal, 226 pubertal), aged 10.14 ± 0.13 years. Participants were classified as obese (n = 267, 52.6%), overweight (n = 174, 34.2%), or of normal BMI (n = 67, 13.2%) according to the International Obesity Task Force (IOTF) cutoff points and were studied prospectively for one year. We demonstrated that LTL increased significantly after 1 year of the lifestyle interventions, irrespective of gender, pubertal status, or body mass index (BMI). Waist circumference was the best negative predictor of LTL at initial assessment. The implementation of the lifestyle interventions also resulted in a significant improvement in clinical (BMI, BMI z-score and waist to height ratio) and body composition indices of obesity, inflammatory markers, hepatic enzymes, glycated hemoglobin (HbA1C), quantitative insulin sensitivity check index (QUICKI), and lipid profile in all participants. These findings indicate that the increased LTL may be associated with a more favorable metabolic profile and decreased morbidity later in life.

The Effect of a Life-Style Intervention Program of Diet and Exercise on Irisin and FGF-21 Concentrations in Children and Adolescents with Overweight and Obesity.

Overweight and obesity in childhood and adolescence represent major public health problems of our century, and account for increased morbidity and mortality in adult life. Irisin and Fibroblast Growth Factor 21 (FGF-21) have been proposed as prognostic and/or diagnostic biomarkers in subjects with obesity and metabolic syndrome, because they increase earlier than other traditional biomarkers. We determined the concentrations of Irisin and FGF-21 in children and adolescents with overweight and obesity before and after one year of a life-style intervention program of diet and physical exercise and explored the impact of body mass index (BMI) reduction on the concentrations of Irisin, FGF-21 and other cardiometabolic risk factors. Three hundred and ten (n = 310) children and adolescents (mean age ± SD: 10.5 ± 2.9 years) were studied prospectively. Following one year of the life-style intervention program, there was a significant decrease in BMI (p = 0.001), waist-to-hip ratio (p = 0.024), waist-to-height ratio (p = 0.024), and Irisin concentrations (p = 0.001), and an improvement in cardiometabolic risk factors. There was no alteration in FGF-21 concentrations. These findings indicate that Irisin concentrations decreased significantly as a result of BMI reduction in children and adolescents with overweight and obesity. Further studies are required to investigate the potential role of Irisin as a biomarker for monitoring the response to lifestyle interventions and for predicting the development of cardiometabolic risk factors.