Association of Apelin Levels in Overweight-obese Children with Pubertal Development, but Not with Insulin Sensitivity: 6.5 Years Follow up Evaluation

ABSTRACT

Background

Obesity in youth is associated with increased risk of metabolic disorders. Adipose tissue hormones are involved in body-weight regulation. Among these, apelin is recognized as an insulin-sensitizer adipokine. Data on apelin levels in obese children and its relation to insulin-sensitivity are limited.

Objective

We aimed to evaluate apelin levels in relation to obesity and insulin sensitivity in a large cohort of overweight/obese children and adolescents. Furthermore, these youths were reevaluated after a median 6.5 years of follow-up, thus allowing assessing changes in apelin levels in relation to increasing age and weight changes.

Methods

Clinical data in 909 children and adolescents were collected between 2007 and 2010. Two hundred and one were reexamined at a median 6.5 years of follow-up. All subjects at baseline and at follow-up underwent an OGTT. Apelin levels were measured on sera by ELISA method.

Results

At baseline, lower apelin levels were associated with increasing age and puberty (Tanner ≥II 0.67 ± 0.96 ng/mL vs. Tanner I 0.89 ± 1.13 ng/mL, p < .002), but not with body-weight. At follow-up, apelin levels in the 201 subjects reexamined were significantly lower than at baseline (0.45 ± 0.77 ng/mL at follow-up, 0.68 ± 0.95 ng/mL baseline, p < .001), confirming the effects of age and puberty. Body-weight did not affect apelin levels. Multiple regression analysis confirmed that sex and puberty were associated with lower apelin levels, independently from age and insulin-sensitivity.

Conclusions

Apelin levels decrease significantly with pubertal development, whilst body-weight in children and adolescents did not determine changes in apelin. Reduced levels of apelin in children and adolescents may therefore represent a necessary response to maintain the “physiological” insulin resistance of puberty.

Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; G: glucose; BMI: Body mass index; DBP: Diastolic blood pressure; ELISA: enzyme-linked immunosorbent assay; HDL-C: High-density lipoprotein-cholesterol; HOMA-B: Homeostatic model assessment for beta-cell function; HOMA-IR: Homeostatic model assessment of insulin-resistance; INS: Insulin; ISI: insulin-sensitivity index; LDL-C: Low-density lipoprotein cholesterol; NW: normal weight; OB: obese; OGTT: oral glucose tolerance test; OW: overweight; SBP: Systolic blood pressure; TC: Total cholesterol; TGs: Triglycerides

KEYWORDS:

• Adipokines
• children
• adolescents
• body-weight
• longitudinal study
• Tanner

Acknowledgments

Particular thanks to V.M. Cambuli, T. Congiu, C. Serafini, C. Satta, L. Perra, F. Scano, A. Strazzera (University Policlinic of Cagliari, Italy).

Disclosure Statement

The authors report no conflict of interest.

Author Contributions

LB, FS, MI and MGB developed the research question and designed this study.

EC, SL, MGP and FD were responsible for data collection and database organization, in collaboration with FAC, DB, IB and ACM. Experimental analyses were performed by MI and FD. All authors had full access to all the data (including statistical reports and tables) and made substantial contributions to the analysis and interpretation of data. The paper was written by LB, FS, MI and MGB. AL, MGC and EC revised the manuscript critically for important intellectual content. All authors have approved the final version of the manuscript.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by research grants from the Regione Autonoma della Sardegna (Grant RAS 2012 n. CRP-59453), and from the Foundation Banca d’Italia (projects 2015), all awarded to Marco G. Baroni, and from the Sapienza University of Rome “Avvio alla Ricerca” grant to Laura Bertoccini.