Circulating progranulin in human infants: relation to prenatal growth and early postnatal nutrition.
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
16
12
2022
accepted:
15
03
2023
revised:
04
03
2023
medline:
24
8
2023
pubmed:
9
4
2023
entrez:
8
4
2023
Statut:
ppublish
Résumé
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). 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 37031297
doi: 10.1038/s41390-023-02595-1
pii: 10.1038/s41390-023-02595-1
doi:
Substances chimiques
Progranulins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1189-1194Informations de copyright
© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
Références
Bateman, A., Cheung, S. T. & Bennett, H. P. J. A brief overview of progranulin in health and disease. Methods Mol. Biol. 1806, 3–15 (2018).
doi: 10.1007/978-1-4939-8559-3_1
pubmed: 29956265
Rhinn, H., Tatton, N., McCaughey, S., Kurnellas, M. & Rosenthal, A. Progranulin as a therapeutic target in neurodegenerative diseases. Trends Pharmacol. Sci. 43, 641–652 (2022).
doi: 10.1016/j.tips.2021.11.015
pubmed: 35039149
Fu, W., Hettinghouse, A. & Liu, C. J. In vitro physical and functional interaction assays to examine the binding of progranulin derivative Atsttrin to TNFR2 and its Anti-TNFα activity. Methods Mol. Biol. 2248, 109–119 (2021).
doi: 10.1007/978-1-0716-1130-2_8
pubmed: 33185871
pmcid: 8112733
Korolczuk, A. & Bełtowski, J. Progranulin, a new adipokine at the crossroads of metabolic syndrome, diabetes, dyslipidemia and hypertension. Curr. Pharm. Des. 23, 1533–1539 (2017).
doi: 10.2174/1381612823666170124114524
pubmed: 28120721
Abella, V. et al. Progranulin as a biomarker and potential therapeutic agent. Drug Discov. Today 22, 1557–1564 (2017).
doi: 10.1016/j.drudis.2017.06.006
pubmed: 28651064
Matsubara, T. et al. PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue. Cell Metab. 15, 38–50 (2012).
doi: 10.1016/j.cmet.2011.12.002
pubmed: 22225875
Li, H. et al. Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner. Cell Cycle 14, 1893–1907 (2015).
doi: 10.1080/15384101.2015.1041686
pubmed: 26039714
pmcid: 4615047
Nguyen, A. D., Nguyen, T. A., Martens, L. H., Mitic, L. L. & Farese, R. V. Jr. Progranulin: at the interface of neurodegenerative and metabolic diseases. Trends Endocrinol. Metab. 24, 597–606 (2013).
doi: 10.1016/j.tem.2013.08.003
pubmed: 24035620
Qu, H., Deng, H. & Hu, Z. Plasma progranulin concentrations are increased in patients with type 2 diabetes and obesity and correlated with insulin resistance. Mediators Inflamm. 2013, 360190 (2013).
doi: 10.1155/2013/360190
pubmed: 23476101
pmcid: 3588183
Tanaka, Y., Takahashi, T. & Tamori, Y. Circulating progranulin level is associated with visceral fat and elevated liver enzymes: significance of serum progranulin as a useful marker for liver dysfunction. Endocr. J. 61, 1191–1196 (2014).
doi: 10.1507/endocrj.EJ14-0210
pubmed: 25231693
Blüher, M. et al. Two patterns of adipokine and other biomarker dynamics in a long-term weight loss intervention. Diabetes Care 35, 342–349 (2012).
doi: 10.2337/dc11-1267
pubmed: 22190676
pmcid: 3263919
Alissa, E. M., Sutaih, R. H., Kamfar, H. Z., Alagha, A. E. & Marzouki, Z. M. Serum progranulin levels in relation to insulin resistance in childhood obesity. J. Pediatr. Endocrinol. Metab. 30, 1251–1256 (2017).
doi: 10.1515/jpem-2017-0321
pubmed: 29176029
Daxer, J. et al. Nocturnal levels of chemerin and progranulin in adolescents: influence of sex, body mass index, glucose metabolism and sleep. J. Pediatr. Endocrinol. Metab. 30, 57–61 (2017).
doi: 10.1515/jpem-2016-0378
pubmed: 27941174
Niklowitz, P., Rothermel, J., Lass, N., Barth, A. & Reinehr, T. Is there a link between progranulin, obesity, and parameters of the metabolic syndrome in children? Findings from a longitudinal intervention study. Pediatr. Diabetes 20, 1047–1055 (2019).
doi: 10.1111/pedi.12915
pubmed: 31469472
Waluga-Kozlowska, E. et al. Progranulin and chemerin plasma level in obese patients with type 2 diabetes treated with a long-acting insulin analogue and premixed insulin analogue. J. Physiol. Pharmacol. 72, https://doi.org/10.26402/jpp.2021.6.07 (2021).
Yilmaz, Y. et al. Serum progranulin as an independent marker of liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease. Dis. Markers 31, 205–210 (2011).
doi: 10.1155/2011/126240
pubmed: 22045426
pmcid: 3826876
Serdar Açıkgöz, A. et al. Evaluation of maternal serum progranulin levels in normotensive pregnancies, and pregnancies with early- and late-onset preeclampsia. J. Matern. Fetal Neonatal Med. 29, 2658–2664 (2016).
pubmed: 26482292
Nobili, V., Alisi, A., Panera, N. & Agostoni, C. Low birth weight and catch-up-growth associated with metabolic syndrome: a ten-year systematic review. Pediatr. Endocrinol. Rev. 6, 241–247 (2008).
pubmed: 19202511
Leunissen, R. W., Kerkhof, G. F., Stijnen, T. & Hokken-Koelega, A. Timing and tempo of first-year rapid growth in relation to cardiovascular and metabolic risk profile in early adulthood. JAMA 301, 2234–2242 (2009).
doi: 10.1001/jama.2009.761
pubmed: 19491185
Nakano, Y. Adult-onset diseases in low birth weight infants: association with adipose tissue maldevelopment. J. Atheroscler. Thromb. 27, 397–405 (2020).
doi: 10.5551/jat.RV17039
pubmed: 31866623
pmcid: 7242223
de Zegher, F. et al. Breast-feeding vs formula-feeding for infants born small-for-gestational-age: divergent effects on fat mass and on circulating IGF-I and high-molecular-weight adiponectin in late infancy. J. Clin. Endocrinol. Metab. 98, 1242–1247 (2013).
doi: 10.1210/jc.2012-3480
pubmed: 23365126
de Zegher, F. et al. Body composition and circulating high-molecular-weight adiponectin and IGF-I in infants born small for gestational age: breast- versus formula-feeding. Diabetes 61, 1969–1973 (2012).
doi: 10.2337/db11-1797
pubmed: 22648385
pmcid: 3402297
Díaz, M. et al. Placental and cord blood methylation of genes involved in energy homeostasis: association with fetal growth and neonatal body composition. Diabetes 66, 779–784 (2017).
doi: 10.2337/db16-0776
pubmed: 27986832
Díaz, M., Garde, E., Lopez-Bermejo, A., de Zegher, F. & Ibañez, L. Differential DNA methylation profile in infants born small-for-gestational-age: association with markers of adiposity and insulin resistance from birth to age 24 months. BMJ Open Diabetes Res. Care 8, e001402 (2013).
doi: 10.1136/bmjdrc-2020-001402
Díaz, M. et al. Circulating GLP-1 in infants born small-for-gestational-age: breast-feeding versus formula-feeding. Int. J. Obes. 39, 1501–1503 (2015).
doi: 10.1038/ijo.2015.117
Díaz, M., García-Beltran, C., López-Bermejo, A., de Zegher, F. & Ibáñez, L. GLP-1 and IGF-I levels are elevated in late infancy in low birth weight infants, independently of GLP-1 receptor polymorphisms and neonatal nutrition. Int. J. Obes. 42, 915–918 (2018).
doi: 10.1038/ijo.2017.271
Díaz, M. et al. Circulating growth-and-differentiation factor-15 in early life: relation to prenatal and postnatal growth and adiposity measurements. Pediatr. Res. 87, 897–902 (2020).
doi: 10.1038/s41390-019-0633-z
pubmed: 31645058
Konopka, J., Richbourgh, B. & Liu, C. The role of PGRN in musculoskeletal development and disease. Front. Biosci. 19, 662–671 (2014).
doi: 10.2741/4234
Gow, D. J., Sester, D. P. & Hume, D. A. CSF-1, IGF-1, and the control of postnatal growth and development. J. Leukoc. Biol. 88, 475–481 (2010).
doi: 10.1189/jlb.0310158
pubmed: 20519640
Hu, S. Y., Tai, C. C., Li, Y. H. & Wu, J. L. Progranulin compensates for blocked IGF-1 signaling to promote myotube hypertrophy in C2C12 myoblasts via the PI3K/Akt/mTOR pathway. FEBS Lett. 586, 3485–3492 (2012).
doi: 10.1016/j.febslet.2012.07.077
pubmed: 22967900
Noguchi, T. et al. Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice. Biochem. Biophys. Res. Commun. 465, 638–643 (2015).
doi: 10.1016/j.bbrc.2015.08.077
pubmed: 26297947
Wang, N., Zhang, J. & Yang, J.X. Growth factor progranulin blocks tumor necrosis factor-α-mediated inhibition of osteoblast differentiation. Genet. Mol. Res. 15, https://doi.org/10.4238/gmr.15038126 (2016).
Zhao, Y. P., Tian, Q. Y., Frenkel, S. & Liu, C. J. The promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling. Biomaterials 34, 6412–6421 (2013).
doi: 10.1016/j.biomaterials.2013.05.030
pubmed: 23746860
pmcid: 3713419
Ding, Y. et al. Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus. Ann. NY Acad. Sci. 1490, 77–89 (2021).
doi: 10.1111/nyas.14568
pubmed: 33543485
Milajerdi, A., Maghbooli, Z., Mohammadi, F., Hosseini, B. & Mirzaei, K. Progranulin concentration in relation to bone mineral density among obese individuals. Arch. Endocrinol. Metab. 62, 179–186 (2018).
pubmed: 29641735
pmcid: 10118980
Wang, L., Roth, T., Nakamura, M. C. & Nissenson, R. A. Female-specific role of progranulin to suppress bone formation. Endocrinology 160, 2024–2037 (2019).
doi: 10.1210/en.2018-00842
pubmed: 31237618
pmcid: 6691684
Lan, Y. J., Sam, N. B., Cheng, M. H., Pan, H. F. & Gao, J. Progranulin as a potential therapeutic target in immune-mediated diseases. J. Inflamm. Res. 14, 6543–6556 (2021).
doi: 10.2147/JIR.S339254
pubmed: 34898994
pmcid: 8655512
Yang, K. D., He, Y., Xiao, S., Ai, Q. & Yu, J. L. Identification of progranulin as a novel diagnostic biomarker for early-onset sepsis in neonates. Eur. J. Clin. Microbiol. Infect. Dis. 39, 2405–2414 (2020).
doi: 10.1007/s10096-020-03981-x
pubmed: 32720089
Rao, L. et al. Progranulin as a novel biomarker in diagnosis of early-onset neonatal sepsis. Cytokine 128, 155000 (2020).
doi: 10.1016/j.cyto.2020.155000
pubmed: 31982701
Jian, J., Konopka, J. & Liu, C. Insights into the role of progranulin in immunity, infection, and inflammation. J. Leukoc. Biol. 93, 199–208 (2013).
doi: 10.1189/jlb.0812429
pubmed: 23089745
pmcid: 3545674
Adela, R. & Banerjee, S. K. GDF-15 as a target and biomarker for diabetes and cardiovascular diseases: a translational prospective. J. Diabetes Res. 2015, 490842 (2015).
doi: 10.1155/2015/490842
pubmed: 26273671
pmcid: 4530250
Wang, D. et al. GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease. Nat. Rev. Endocrinol. 17, 592–607 (2021).
doi: 10.1038/s41574-021-00529-7
pubmed: 34381196