Longitudinal Study of Physiologic Insulin Resistance and Metabolic Changes of Puberty

AbstractIntroduction:Insulin resistance (IR) is the major driver for the development of obesity-associated metabolic and cardiovascular complications. It is well known that IR increase physiologically during puberty; hence, pubertal maturation might favour this metabolic risk in obese children. Recently, a study carried out in adult women with obesity has identified a new adipokine, known as S100A4, strongly associated with IR and inflammation in adipose tissue. On the contrary, little is known about the implication of S100A4 in the development of such metabolic disturbances during the onset and course of pubertal development.Materials and methods:A longitudinal study was conducted on 53 Spanish girls distributed in six experimental conditions according to their obesity and IR status (before (T0) and after (T1) the onset of puberty). Anthropometric and biochemical parameters were evaluated in all samples and time points. Classification of pubertal stage was made according to the Tanner scale. S100A4 protein levels were quantified by ELISA CSB-EL02032HU in plasma samples (Cusabio Biotech, Wuhan, China). The statistical analysis of the results was carried out with the “nlme” package in R v3.4.4, using a mixed-effects linear model with random intercept and slope.Results:At a significance level of alpha = 0.05, a linear mixed-effects model reported a significant association (P = 0.03) between the interaction term “time*experimental group” and S100A4 levels. Post-hoc pairwise comparisons between experimental groups revealed a strong association between a worsening/improvement of the IR status and the increase/decrease of S100A4 levels (yielding significant results for 5 of the 15 comparisons (P = 0.008, P = 0.04, P = 0.02, P = 0.04 and P = 0.02)). Furthermore, a multiple linear regression model reported a positive correlation between the increase in S100A4 levels and the increase in HOMA values during the course of puberty (B = 6.03, SE = 2.66 and P = 0.028).Discussion:The S100A4 protein is strongly associated with the development of IR in girls with childhood obesity and this association is accentuated during pubertal development. Increase in S100A4 levels could be one of the molecular mechanisms by which pubertal maturation favour an increased metabolic risk in children with obesity.

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Altered metabolomic profiling of overweight and obese adolescents after combined training is associated with reduced insulin resistance

Scientific Reports ◽

10.1038/s41598-020-73943-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Renata G. Duft ◽

Alex Castro ◽

Ivan L. P. Bonfante ◽

Wendell A. Lopes ◽

Larissa R. da Silva ◽

...

Keyword(s):

Insulin Resistance ◽

Exercise Training ◽

Dietary Intervention ◽

Metabolic Changes ◽

Fat Free Mass ◽

Control Group ◽

Resonance Spectroscopy ◽

Obese Adolescents ◽

Combined Training ◽

Positive Effects

Abstract Exercise training and a healthy diet are the main non-pharmacological strategies for treating chronic conditions, such as obesity and insulin resistance (IR), in adolescents. However, the isolated metabolic changes caused by exercise training without dietary intervention have not yet been established. We investigated how combined training (CT) without dietary intervention altered the concentrations of serum metabolites, biochemical, anthropometric and functional parameters in overweight and obese adolescents. Thirty-seven adolescents (14.6 ± 1.05 years), of both sexes, were randomly assigned to the control group (CG, n = 19) or the training group (TG, n = 18). The CT was composed by resistance training and aerobic training performed in the same session (~ 60 min), three times a week, for 12 weeks. All assessments were performed pre and post-intervention. Metabolomics analyses were conducted using nuclear magnetic resonance spectroscopy (1H NMR) in a 600 MHz spectrometer. There was a decrease in body weight (BW), body mass index (BMI), waist circumference (WC), % body fat (%BF), fasting glucose, insulin levels, and insulin resistance (IR), by HOMA-IR, in the TG. An increase in fat-free mass (FFM) was also observed in the CG. The metabolic changes were given mainly by changes in the levels of metabolites 2-oxoisocaproate (↓TG), 3-hydroxyisobutyrate (↑CG and ↓TG), glucose (↓TG), glutamine (↓CG and ↑TG) and pyruvate (↓TG). These findings demonstrate the positive effects of CT program without dietary intervention on metabolomic profile, body composition, biochemical markers, and glucose metabolism in overweight and obese adolescents.

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