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Circulating progranulin in human infants: relation to prenatal growth and early postnatal nutrition

Pediatric Research volume 94, pages 1189–1194 (2023)Cite this article

Abstract

Background

Progranulin (PGRN) displays pleiotropic biological functions and has been proposed as a biomarker for metabolic diseases. We longitudinally assessed PGRN concentrations in infants born appropriate (AGA) or small for gestational age (SGA), the latter being at risk for obesity and type 2 diabetes, especially if they experience an excessive postnatal catch-up in weight and are formula-fed (FF).

Methods

The study population consisted of 183 infants who were exclusively breast-fed [(BF), AGA, n = 66; SGA, n = 40], or FF (AGA, n = 31; SGA, n = 46) over the first 4 months. Assessments included auxology, fasting glucose, insulin, IGF-1, high-molecular-weight adiponectin, PGRN and body composition (by DXA), at birth, and at age 4 and 12 months.

Results

PGRN levels were low at birth and unaffected by prenatal growth. PGRN increased at 4 and 12 months, although to a lesser extent in SGA infants, and was unrelated to the mode of feeding. PGRN correlated with markers of adiposity, inflammation and insulin resistance in both AGA and SGA infants, especially in those FF.

Conclusions

The attenuated increase of PGRN levels in SGA infants over the first year of life, along with the association to markers of unhealthy metabolic profile, might point to a role of PGRN in future disease risks.

Impact

  • Progranulin (PGRN) displays pleiotropic biological functions and has been proposed as a biomarker for metabolic diseases.

  • In healthy infants, PGRN concentrations are low at birth and experience a significant and progressive increase up to age 12 months, which is less marked in infants born small for gestational age (SGA) and is unrelated to the mode of feeding.

  • Circulating PGRN is related to markers of adiposity, inflammation, and insulin sensitivity, especially in formula-fed SGA infants.

  • PGRN may play a role in the metabolic adaptations of SGA infants during early life, potentially contributing to the risk for obesity and type 2 diabetes in this population.

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Fig. 1: Longitudinal Progranulin concentrations (mean ± SEM) from birth to age 12 months in children born appropriate-for-gestational-age (AGA, n = 97) or small-for-gestational-age (SGA, n = 86) who were exclusively breast-fed [(BF), AGA, n = 66; SGA, n = 40] or formula-fed [(FF), AGA, n = 31; SGA, n = 46] over the first 4 months.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

M.D., C.L., and L.I. are Clinical Investigators of CIBERDEM (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, ISC III, Madrid, Spain). A.M.-A. and F.V. are Clinical Investigators of CIBEROBN (Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, ISC III, Madrid, Spain). A.L.-B. is a Clinical Investigator of the I3 Fund for Scientific Research (Ministry of Science and Innovation, Spain). F.d.Z. is a clinical investigator from the Clinical Research Council of Leuven University Hospitals, Belgium. F.V. is an ICREA Academia Researcher (Generalitat de Catalunya).

Funding

This study was supported by the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, and by the Fondo Europeo de Desarrollo Regional (FEDER) (PI18/00109), PERIS-SLT017/20/000228, SGR 2021/00659, and grant PID2020-114112RB-100 from MICIN/AEI/10.13039/50110 0011033, Spain.

Author information

Author notes

  1. These authors contributed equally: Marta Díaz, Alberto Mestres-Arenas.

  2. These authors jointly supervised this work: Francesc Villarroya, Lourdes Ibáñez.

Authors and Affiliations

  1. Pediatric Research Institute Sant Joan de Déu, University of Barcelona, 08950, Esplugues, Barcelona, Spain

    Marta Díaz, Carles Lerin & Lourdes Ibáñez

  2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Health Institute Carlos III, Madrid, Spain

    Marta Díaz, Carles Lerin & Lourdes Ibáñez

  3. Biochemistry and Molecular Biomedicine Department, Biomedicine Institute, University of Barcelona, 08028, Barcelona, Spain

    Alberto Mestres-Arenas, Rubén Cereijo & Francesc Villarroya

  4. Network Biomedical Research Center of Physiopathology of Obesity and Nutrition (CIBEROBN), Health Institute Carlos III, 28029, Madrid, Spain

    Alberto Mestres-Arenas & Francesc Villarroya

  5. Research Institute, Hospital de la Santa Creu i de Sant Pau, Barcelona, Spain

    Rubén Cereijo

  6. Department of Pediatrics, Dr. Josep Trueta Hospital, 17007, Girona, Spain

    Abel López-Bermejo

  7. Girona Institute forBiomedical Research, 17007, Girona, Spain

    Abel López-Bermejo

  8. University of Leuven, 3000, Leuven, Belgium

    Francis de Zegher

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  1. Marta Díaz
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Contributions

M.D. researched data, contributed to study design and data interpretation, wrote the manuscript, and reviewed/edited the manuscript. A.M.-A. researched data, contributed to data interpretation, and reviewed/edited the manuscript. C.L. reviewed/edited the manuscript. R.C. researched data, contributed to data interpretation, and reviewed/edited the manuscript. A.L.-B. reviewed/edited the manuscript. F.d.Z. contributed to data interpretation and reviewed/edited the manuscript. F.V. contributed to data interpretation, wrote the manuscript, and reviewed/edited the manuscript. L.I. contributed to study design and data interpretation, wrote the manuscript, and reviewed/edited the manuscript.

Corresponding authors

Correspondence to Francesc Villarroya or Lourdes Ibáñez.

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Díaz, M., Mestres-Arenas, A., Lerin, C. et al. Circulating progranulin in human infants: relation to prenatal growth and early postnatal nutrition. Pediatr Res 94, 1189–1194 (2023). https://doi.org/10.1038/s41390-023-02595-1

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