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The metabolic implications of aquaporin 7 (AQP7) promoter variants in lean children and children with obesity

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Abstract

Purpose

AQP7, a water/glycerol transporting protein, regulates adipocyte glycerol efflux and influences lipid and glucose homeostasis. Altered AQP7 expression in adults leads to impaired glycerol dynamics, adipocyte hypertrophy, and a predisposition to obesity and diabetes. AQP7 gene promoter variants lead to impaired AQP7-mediated adipocyte glycerol efflux and adipocyte hypertrophy. To assess its possible involvement in childhood obesity and metabolic abnormalities, the AQP7 promoter was studied in order to identify possible mutations and/or polymorphisms in children.

Methods

Genomic DNA was extracted from the blood of 61 lean children (BMI < 85%) (46 prepubertal and 15 pubertal) and 41 children with obesity (BMI > 95%) (22 prepubertal and 19 pubertal). The samples were sequenced for AQP7 promoter region − 2580 (2421) to − 1161 (3840) using Automated Sanger sequence analysis.

Results

One novel mutation −2185 (T2816A) was found in an obese prepubertal child with low AQP7 mRNA expression, high levels of serum glycerol, and low serum insulin levels. The novel single nucleotide polymorphisms (SNPs) − 2291 (A2710G), − 2219 (C2782A), − 2091 (C2910A), and – 1932 (G3069A) were identified, together with the previously described SNP – 1884 (C3117T), rs3758268. The heterozygous state and the recessive allele of all four SNPs were related to a positive family history of diabetes mellitus type 2 (p = 0.001).

Conclusions

The novel mutation – 2185 (T2816A) might be associated with the lower gene expression of AQP7 and high levels of serum glycerol that possibly contribute to the obese phenotype. The heterozygous genotype of the four SNPs – 2291 (A2710G), − 2219 (C2782A), − 2091 (C2910A), and – 1884 (C3117T) in children may be related to a familial predisposition to diabetes mellitus type 2.

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Funding

IKY fellowships research grant of excellence for postgraduate studies in Greece – Siemens program (Grant number SPhD/11230/13β).

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Authors and Affiliations

  1. Department of Paediatrics, Research Laboratory of the Division of Paediatric Endocrinology and Diabetes, University of Patras School of Medicine, 26504, Patras, Greece

    Eleni Oikonomou, Eirini Kostopoulou & Bessie E. Spiliotis

  2. Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Tripoli, Lakonias, Greece

    Andrea Paola Rojas-Gil

  3. Department of Paediatric Surgery, Karamandaneio Children’s Hospital, Patras, Greece

    George Georgiou

Authors
  1. Eleni Oikonomou
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  2. Eirini Kostopoulou
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  3. Andrea Paola Rojas-Gil
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  4. George Georgiou
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  5. Bessie E. Spiliotis
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Contributions

Bessie E. Spiliotis and Eleni Oikonomou conceived/designed the original experiments. George Georgiou enrolled patients and contributed the material from the surgical procedures. Bessie E. Spiliotis contributed the reagents, materials, and laboratory. Eleni Oikonomou performed the experiments. Bessie E. Spiliotis, Eirini Kostopoulou, and Andrea Paola Rojas-Gil supervised the experiments. Eleni Oikonomou analyzed the data of the original studies. Eirini Kostopoulou, Andrea Paola Rojas-Gil, and Bessie E. Spiliotis supervised and checked the statistical analysis of the data. Eleni Oikonomou and Bessie E. Spiliotis wrote the first draft of the manuscript. Eleni Oikonomou, Eirini Kostopoulou, Andrea Paola Rojas-Gil, and Bessie E. Spiliotis contributed to the writing of the final manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Bessie E. Spiliotis.

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The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee of the “Karamandaneio” Children’s Hospital of Patras, Greece. All procedures performed were in accordance with the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed parental consent and children’s assent were obtained in all cases.

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The authors have nothing to disclose.

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Oikonomou, E., Kostopoulou, E., Rojas-Gil, A.P. et al. The metabolic implications of aquaporin 7 (AQP7) promoter variants in lean children and children with obesity. Hormones 19, 187–195 (2020). https://doi.org/10.1007/s42000-020-00184-z

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  • DOI: https://doi.org/10.1007/s42000-020-00184-z

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