Abstract
Background:
Progranulin is an adipokine that is involved in the inflammatory response, glucose metabolism, insulin resistance, and may therefore be involved in chronic subclinical inflammation associated with the pathogenesis of childhood obesity. We aimed to investigate the association of circulating progranulin levels with metabolic parameters in children and to assess the importance of progranulin as a biomarker for metabolic diseases.
Methods:
A total of 150 children were consecutively recruited from the Pediatric Nutrition Clinics at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Children were classified into four groups based on quartile for serum progranulin. Anthropometric variables were measured in all study subjects. Fasting blood samples were collected for measurement of blood glucose, insulin and lipid profile.
Results:
Children within the upper quartile for serum progranulin concentration were heavier, more insulin resistant and had higher concentrations of serum total cholesterol, triglycerides, insulin and high sensitivity C reactive protein compared to those in the lower quartile. On correlation analysis, serum progranulin concentrations were significantly related to general and central adiposity, metabolic parameters, markers of inflammation and insulin resistance. Stepwise multiple regression showed that 26.6% of the variability in serum progranulin could be explained by measures of adiposity.
Conclusions:
The increased serum progranulin concentrations were closely related to measures of adiposity, metabolic parameters, inflammatory marker and insulin resistance indices, suggesting that progranulin may be an excellent biomarker for obesity in childhood.
Acknowledgments
The authors thank all of the patients who participated in or collaborated with the present study. The authors wish to thank Professor Ghazi Jamjom for technical help. The authors wish to thank Professor Gordon Ferns (Brighton and Sussex Medical School, University of Brighton, UK) for a critical review of the manuscript.
Author contributions: EA and ZM designed the research; AA and HK provided cases; RS conducted subject recruitments and data collection; EA analyzed data and wrote the paper; EA had primary responsibility for final content. All authors read and approved the final manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world – a growing challenge. N Engl J Med 2007;356:213–5.10.1056/NEJMp068177Search in Google Scholar PubMed
2. Finucane MM, Stevens GA, Cowan M, Danaei G, Lin JK, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 2011;377:557–67.10.1016/S0140-6736(10)62037-5Search in Google Scholar PubMed
3. Elmaogullari S, Demirel F, Hatipoglu N. Risk factors that affect metabolic health status in obese children. J Pediatr Endocrinol Metab 2017;30:49–55.10.1515/jpem-2016-0128Search in Google Scholar PubMed
4. van Emmerik NM, Renders CM, van de Veer M, van Buuren S, van der Baan-Slootweg OH, et al. High cardio-vascular risk in severely obese young children and adolescents. Arch Dis Child 2012;97:818–21.10.1136/archdischild-2012-301877Search in Google Scholar PubMed
5. Cao H. Adipocytokines in obesity and metabolic disease. J Endocrinol 2014;220:T47–59.10.1530/JOE-13-0339Search in Google Scholar PubMed PubMed Central
6. Anderson PD, Mehta NN, Wolfe ML, Hinkle CC, Pruscino L, et al. Innate immunity modulates adipokines in humans. J Clin Endocrinol Metab 2007;92:2272–9.10.1210/jc.2006-2545Search in Google Scholar PubMed
7. Mancuso P. The role of adipokines in chronic inflammation. Immunotargets Ther 2016;5:47–56.10.2147/ITT.S73223Search in Google Scholar PubMed PubMed Central
8. Matsubara T, Mita A, Minami K, Hosooka T, Kitazawa S, et al. PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue. Cell Metab 2012;15:38–50.10.1016/j.cmet.2011.12.002Search in Google Scholar PubMed
9. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 2011;11:85–97.10.1038/nri2921Search in Google Scholar PubMed PubMed Central
10. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. Br Med J 2000;320:1240–3.10.1136/bmj.320.7244.1240Search in Google Scholar PubMed PubMed Central
11. Li C, Ford S, Mokdad AH, Cook S. Recent trends in waist circumference and waist-height ratio among US children and adolescents. Pediatr 2006;118:1390–8.10.1542/peds.2006-1062Search in Google Scholar PubMed
12. Frayn KN. Insulin resistance, impaired postprandial lipid metabolism and abdominal obesity. A deadly triad. Med Princ Pract 2002;11:31–40.10.1159/000066414Search in Google Scholar PubMed
13. Tönjes A, Fasshauer M, Kratzsch J, Stumvoll M, Blüher M. Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes. PLoS One 2010;5:e13911.10.1371/journal.pone.0013911Search in Google Scholar PubMed PubMed Central
14. Deng Y, Scherer PE. Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci 2010;1212:E1–19.10.1111/j.1749-6632.2010.05875.xSearch in Google Scholar PubMed PubMed Central
15. Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 2011;332:478–84.10.1126/science.1199214Search in Google Scholar PubMed PubMed Central
16. Finch N, Baker M, Crook R, Swanson K, Kuntz K, et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain 2009;132:583–91.10.1093/brain/awn352Search in Google Scholar PubMed PubMed Central
17. Youn BS, Bang SI, Klöting N, Park JW, Lee N, et al. Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes 2009;58:627–36.10.2337/db08-1147Search in Google Scholar PubMed PubMed Central
18. Valérie W, Jean-Denis F, Marisa V, Jean-François M, Emmanuel Le P, et al. Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med 2003;198:977–85.10.1084/jem.20030382Search in Google Scholar PubMed PubMed Central
19. Daniel E, He Z, Bateman A. Progranulin (acrogranin/PC cell-derived growth factor/granulin-epi- thelin precursor) is expressed in the placenta, epidermis, microvasculature, and brain during murine development. Dev Dynam 2003;227:593–9.10.1002/dvdy.10341Search in Google Scholar PubMed
20. Klöting N, Fasshauer M, Dietrich A, Kovacs P, Schön MR, et al. Insulin sensitive obesity. Am J Physiol Endocrinol Metab 2010;299:E506–15.10.1152/ajpendo.00586.2009Search in Google Scholar PubMed
21. Yilmaz Y, Eren F, Yonal O, Polat Z, Bacha M, et al. Serum progranulin as an independent marker of liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease. Dis Markers 2011;31:205–10.10.1155/2011/126240Search in Google Scholar PubMed
22. Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes 2009;33:54–66.10.1038/ijo.2008.229Search in Google Scholar PubMed PubMed Central
23. Guerra R, Kriazhev L, Hernandez-Blazquez F, Bateman A. Progranulin is a stress-response factor in fibroblasts subjected to hypoxia and acidosis. Growth Factors 2007;25:280–5.10.1080/08977190701781222Search in Google Scholar PubMed
24. Brar PC, Patel P, Katz S. The relationship between insulin resistance and endothelial dysfunction in obese adolescents. J Pediatr Endocrinol Metab 2017;30:635–42.10.1515/jpem-2016-0404Search in Google Scholar PubMed
25. He Z, Ong CH, Halper J, Bateman A. Progranulin is a mediator of the wound response. Nat Med 2003;9:225–9.10.1038/nm816Search in Google Scholar PubMed
©2017 Walter de Gruyter GmbH, Berlin/Boston
