Ependymin-related protein 1 levels are elevated in children with obesity and correlated with metabolic disorders

Abstract

Ependymin-related protein 1 (EPDR1) has been found in the secretory body of adipocytes where it plays a role in lipid binding, transportation, and catabolism. The aim of this study was to investigate serum EPDR1 levels in children with obesity and normal-weight children and to compare the levels of EPDR1 between children with obesity, with and without metabolic-associated fatty liver disease (MAFLD). Thirty-four normal-weight children and 49 children with obesity (15 with MAFLD) were included in the study. Circulating EPDR1, IL-1β, and TNF-α were measured using enzyme-linked immunosorbent assays. Anthropometric and biochemical measurements related to obesity, blood lipids, and insulin resistance were performed on all participants. The serum EPDR1 levels of children with obesity were significantly higher than those of the control group. There was no difference in EPDR1 levels between the patients with and without MAFLD. Circulating EPDR1 was positively correlated with body mass index (BMI), BMI z-score, insulin, glucose, homeostatic model assessment insulin resistance index (HOMA-IR), triglycerides, white blood cells, and neutrophils. Binary logistic regression analysis showed a significant increase in the odds ratio of obesity with increasing EPDR1 levels. EPDR1 is strongly associated with obesity and may also be associated with metabolic disorders. This trial is registered with ChiCTR2300070951.

Keywords

children with obesity / Ependymin-Related Protein 1 / metabolic associated fatty liver disease / metabolic disorders

References

[1] Kubo T. Common approach to childhood obesity in Japan. J Pediatr Endocrinol Metab. 2014;27(7-8):581-592.

[2] Skinner AC, Ravanbakht SN, Skelton JA, Perrin EM, Armstrong SC. Prevalence of obesity and severe obesity in US children, 1999-2016. Pediatrics. 2018;141(3):141.

[3] Poyrazoglu S, Bas F, Darendeliler F. Metabolic syndrome in young people. Curr Opin Endocrinol Diabetes Obes. 2014;21(1):56-63.

[4] Aggarwal A, Puri K, Thangada S, Zein N, Alkhouri N. Nonalcoholic fatty liver disease in children: recent practice guidelines, where do they take us?Curr Pediatr Rev. 2014;10(2):151-161.

[5] Shah S, Kublaoui BM, Oden JD, White PC. Screening for type 2 diabetes in obese youth. Pediatrics. 2009;124(2):573-579.

[6] Gunatilake RP, Perlow JH. Obesity and pregnancy: clinical management of the obese gravida. Am J Obstet Gynecol. 2011;204(2):106-119.

[7] Malpique R, Gallego-Escuredo JM, Sebastiani G, et al. Brown adipose tissue in prepubertal children: associations with sex, birthweight, and metabolic profile. Int J Obes. 2019;43(2):384-391.

[8] Huang JS, Barlow SE, Quiros-Tejeira RE, et al. Childhood obesity for pediatric gastroenterologists. J Pediatr Gastroenterol Nutr. 2013;56(1):99-109.

[9] Benedict M, Zhang X. Non-alcoholic fatty liver disease: an expanded review. World J Hepatol. 2017;9(16):715-732.

[10] Chandler M, Cunningham S, Lund EM, et al. Obesity and associated comorbidities in people and companion animals: a one health perspective. J Comp Pathol. 2017;156(4):296-309.

[11] Mahabir S. Is nonalcoholic fatty liver disease driving the increased incidence of liver cancer?Cancer. 2016;122(14):2277-2278.

[12] Georgoulis M, Kontogianni MD, Tileli N, et al. The impact of cereal grain consumption on the development and severity of non-alcoholic fatty liver disease. Eur J Nutr. 2014;53(8):1727-1735.

[13] Shashoua VE. Ependymin, a brain extracellular glycoprotein, and CNS plasticity. Ann N Y Acad Sci. 1991;627(1 Activity-Driv):94-114.

[14] Deshmukh AS, Peijs L, Beaudry JL, et al. Proteomics-based comparative mapping of the secretomes of human Brown and white adipocytes reveals EPDR1 as a novel batokine. Cell Metab. 2019;30(5):963-975.

[15] Park JK, Kim KY, Sim YW, et al. Structures of three ependymin-related proteins suggest their function as a hydrophobic molecule binder. IUCrJ. 2019;6(Pt 4):729-739.

[16] Kolter T, Sandhoff K. Lysosomal degradation of membrane lipids. FEBS Lett. 2010;584(9):1700-1712.

[17] Schulze H, Sandhoff K. Sphingolipids and lysosomal pathologies. Biochim Biophys Acta. 2014;1841(5):799-810.

[18] Wei Y, Xiong ZJ, Li J, et al. Crystal structures of human lysosomal EPDR1 reveal homology with the superfamily of bacterial lipoprotein transporters. Commun Biol. 2019;2(1):52.

[19] Kollmann K, Mutenda KE, Balleininger M, et al. Identification of novel lysosomal matrix proteins by proteome analysis. Proteomics. 2005;5(15):3966-3978.

[20] Ye F, Zhang H, Yang YX, et al. Comparative proteome analysis of 3T3-L1 adipocyte differentiation using iTRAQ-coupled 2D LC-MS/MS. J Cell Biochem. 2011;112(10):3002-3014.

[21] Lee P, Linderman JD, Smith S, et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 2014;19(2):302-309.

[22] Stanford KI, Middelbeek RJ, Townsend KL, et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest. 2013;123(1):215-223.

[23] Svensson KJ, Long JZ, Jedrychowski MP, et al. A secreted Slit2 fragment regulates adipose tissue thermogenesis and metabolic function. Cell Metab. 2016;23(3):454-466.

[24] Bollepalli S, Kaye S, Heinonen S, et al. Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss. Int J Obes. 2018;42(3):412-423.

[25] Sikaris KA. The clinical biochemistry of obesity. Clin Biochem Rev. 2004;25(3):165-181.

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2023 2023 The Authors. Pediatric Discovery published by John Wiley & Sons Australia, Ltd on behalf of Children's Hospital of Chongqing University.