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Association of chemerin gene promoter methylation in maternal blood and breast milk during gestational diabetes

Part of: Diabetes and DOHaD

Published online by Cambridge University Press:  30 March 2021

Syeda Sadia Fatima Open the ORCID record for Syeda Sadia Fatima [Opens in a new window] ,
Rehana Rehman ,
Jibran Sualeh Muhammad ,
Russell Martins ,
Nuruddin Mohammed Open the ORCID record for Nuruddin Mohammed [Opens in a new window]  and
Unab Khan
Syeda Sadia Fatima*
Affiliation:
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, 74800, Pakistan
Rehana Rehman
Affiliation:
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, 74800, Pakistan
Jibran Sualeh Muhammad
Affiliation:
Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
Russell Martins
Affiliation:
Medical College, Aga Khan University, Karachi, 74800, Pakistan
Nuruddin Mohammed
Affiliation:
Department of Obstetrics and Gynecology, Aga Khan University, Karachi, 74800, Pakistan
Unab Khan
Affiliation:
Department of Family Medicine, Aga Khan University, Karachi, 74800, Pakistan
*
Address for correspondence: Dr. Syeda Sadia Fatima, Assistant Professor (Physiology), Department of Biological and Biomedical Sciences, Aga Khan University, Stadium Road, Karachi 74800, Pakistan. Email: sadia.fatima@aku.edu
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Abstract

The intrauterine environment and early-life nutrition are regulated by maternal biomarkers in the blood and breast milk. We aimed to explore epigenetic modifications that may contribute to differential chemerin expression in maternal plasma, colostrum, and breast milk and find its association with fetal cord blood and infant weight at 6 weeks postpartum. Thirty-three gestational diabetes mellitus (GDM) mothers and 33 normoglycemic mothers (NGT) were recruited. Two maternal blood samples (28th week of gestation and 6 weeks postpartum), cord blood, colostrum, and mature milk were collected. Methylation-specific polymerase chain reaction and enzyme-linked immunosorbent assay were conducted. The weight of the babies was measured at birth and 6 weeks postpartum. Serum chemerin levels at the 28th gestational week and 6 weeks postpartum were significantly lower for the NGT group as compared to the GDM group; (P < 0.05). Higher colostrum chemerin concentrations were observed in the GDM group and remained elevated in mature milk as compared to NGT (P < 0.05). Colostrum and breast milk chemerin levels showed an independent association with infant weight at 6 weeks postpartum (r = 0.270; P = 0.034) (r = 0.464; P < 0.001). Forty percent GDM mothers expressed unmethylated chemerin reflecting increased chemerin concentration in the maternal blood. This pattern was also observed in newborn cord blood where 52% of samples showed unmethylated chemerin in contrast to none in babies born to normoglycemic mothers. The results of this study highlight the critical importance of altered chemerin regulation in gestational diabetic mothers and its effect during early life period and suggest a possible role in contributing to childhood obesity.

Keywords

Breast milk adipokinegestational diabetesinfant weightchemerinobesity

Information

Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 1 , February 2022 , pp. 108 - 114
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Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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References

Agosti, M, Tandoi, F, Morlacchi, L, Bossi, A. Nutritional and metabolic programming during the first thousand days of life. La Pediatria Medica e Chirurgica. 2017; 39, 157. https://doi.org/10.4081/pmc.2017.157 CrossRefGoogle ScholarPubMed
Moore, V, Miller, A, Boulton, T, et al. Placental weight, birth measurements, and blood pressure at age 8 years. Arch Dis Childhood. 1996; 74, 538–541.CrossRefGoogle ScholarPubMed
Barker, D, Bull, AR, Osmond, C, Simmonds, SJ. Fetal and placental size and risk of hypertension in adult life. BMJ. 1990; 301, 259–262.CrossRefGoogle ScholarPubMed
Forsen, T, Eriksson, J, Tuomilehto, J, Reunanen, A, Osmond, C, Barker, D. The fetal and childhood growth of persons who develop type 2 diabetes. Ann Intern Med. 2000; 133, 176–182.CrossRefGoogle ScholarPubMed
Desoye, G, Nolan, CJ. The fetal glucose steal: an underappreciated phenomenon in diabetic pregnancy. Diabetologia. 2016; 59, 1089–1094.CrossRefGoogle ScholarPubMed
Scholtens, DM, Kuang, A, Lowe, LP, et al. Hyperglycemia and adverse pregnancy outcome follow-up study (HAPO FUS): maternal glycemia and childhood glucose metabolism. Diabetes Care. 2019; 42, 381–392.CrossRefGoogle ScholarPubMed
Sahoo, K, Sahoo, B, Choudhury, AK, Sofi, NY, Kumar, R, Bhadoria, AS. Childhood obesity: causes and consequences. J Fam Med Prim Care. 2015; 4, 187.Google ScholarPubMed
Gupta, N, Shah, P, Nayyar, S, Misra, A. Childhood obesity and the metabolic syndrome in developing countries. Indian J Pediatr. 2013; 80, 28–37.CrossRefGoogle ScholarPubMed
Vos, MB, Welsh, J. Childhood obesity: update on predisposing factors and prevention strategies. Curr Gastro Rep. 2010; 12, 280–287.CrossRefGoogle ScholarPubMed
Garces, MF, Sanchez, E, Ruíz-Parra, AI, et al. Serum chemerin levels during normal human pregnancy. Peptides. 2013; 42, 138–143.CrossRefGoogle ScholarPubMed
Zhao, L, Yamaguchi, Y, Sharif, S, et al. Chemerin158K protein is the dominant chemerin isoform in synovial and cerebrospinal fluids but not in plasma. J Biol Chem. 2011; 286, 39520–39527.CrossRefGoogle Scholar
Bozaoglu, K, Segal, D, Shields, KA, et al. Chemerin is associated with metabolic syndrome phenotypes in a Mexican-American population. J Clin Endocrinol Metal. 2009; 94, 3085–3088.CrossRefGoogle Scholar
Fatima, SS, Alam, F, Chaudhry, B, Khan, TA. Elevated levels of chemerin, leptin and interleukin–18 in gestational diabetes mellitus. J Matern Fetal Neonat Med. 2016; 30, 1023–1028. https://doi.org/10.1080/14767058.2016.1199671 CrossRefGoogle ScholarPubMed
Fatima, SS, Bozaoglu, K, Rehman, R, Alam, F, Memon, AS. Elevated chemerin levels in Pakistani men: an interrelation with metabolic syndrome phenotypes. Plos One. 2013; 8, e57113.CrossRefGoogle ScholarPubMed
Yang, M, Yang, G, Dong, J, et al. Elevated plasma levels of chemerin in newly diagnosed type 2 diabetes mellitus with hypertension. J Investig Med. 2010; 58, 883–886.CrossRefGoogle ScholarPubMed
Hare, KJ, Bonde, L, Svare, JA, et al. Decreased plasma chemerin levels in women with gestational diabetes mellitus. Diabet Med. 2014; 31, 936–940. https://doi.org/10.1111/dme.12436 CrossRefGoogle ScholarPubMed
Barker, G, Lim, R, Rice, GE, Lappas, M. Increased chemerin concentrations in fetuses of obese mothers and correlation with maternal insulin sensitivity. J Matern Fetal Neonat Med. 2012; 25, 2274–2280.CrossRefGoogle ScholarPubMed
Li, XM, Ji, H, Li, CJ, Wang, PH, Yu, P, Yu, DM. Chemerin expression in Chinese pregnant women with and without gestational diabetes mellitus. Ann Endocrinol (Paris). 2015; 76, 19–24. https://doi.org/10.1016/j.ando.2014.10.001 CrossRefGoogle ScholarPubMed
Fatima, SS, Alam, F, Chaudhry, B, Khan, TA. Elevated levels of chemerin, leptin, and interleukin-18 in gestational diabetes mellitus. J Matern Fetal Neonat Med. 2017; 30, 1023–1028. https://doi.org/10.1080/14767058.2016.1199671 CrossRefGoogle ScholarPubMed
Pfau, D, Stepan, H, Kratzsch, J, et al. Circulating levels of the adipokine chemerin in gestational diabetes mellitus. Horm Res Paediatr. 2010; 74, 56–61.CrossRefGoogle ScholarPubMed
Peila, C, Gazzolo, D, Bertino, E, Cresi, F, Coscia, A. Influence of diabetes during pregnancy on human milk composition. Nutrients. 2020; 12, 185.CrossRefGoogle ScholarPubMed
Ustebay, S, Baykus, Y, Deniz, R, et al. Chemerin and dermcidin in human milk and their alteration in gestational diabetes. J Human Lact. 2019; 35, 550–558.CrossRefGoogle ScholarPubMed
Waterland, RA, Jirtle, RL. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition. 2004; 20, 63.CrossRefGoogle ScholarPubMed
Muhammad, JS, Khan, MR, Ghias, K. DNA methylation as an epigenetic regulator of gallbladder cancer: an overview. Intern J Surg. 2018; 53, 178–183.CrossRefGoogle ScholarPubMed
Kwiecien, K, Brzoza, P, Majewski, P, et al. Novel insights into the regulation of chemerin expression: role of acute-phase cytokines and DNA methylation. BioRxiv. 2019. doi: https://doi.org/10.1101/765834.Google Scholar
Bryant, M, Santorelli, G, Lawlor, DA, et al. A comparison of South Asian specific and established BMI thresholds for determining obesity prevalence in pregnancy and predicting pregnancy complications: findings from the Born in Bradford cohort. Inter J Obes. 2014; 38, 444–450.CrossRefGoogle ScholarPubMed
Brunner, S, Schmid, D, Zang, K, et al. Breast milk leptin and adiponectin in relation to infant body composition up to 2 years. Pediatric Obes. 2015; 10, 67–73.CrossRefGoogle ScholarPubMed
Kragstrup, TW, Vorup-Jensen, T, Deleuran, B, Hvid, M. A simple set of validation steps identifies and removes false results in a sandwich enzyme-linked immunosorbent assay caused by anti-animal IgG antibodies in plasma from arthritis patients. SpringerPlus. 2013; 2, 263.CrossRefGoogle Scholar
Beckers, J, Teperino, R, Hérault, Y, de Angelis, MH. Introduction to mammalian genome special issue: epigenetics. Mamm Genome. 2020; 31, 117–118. https://doi.org/10.1007/s00335-020-09843-3 CrossRefGoogle ScholarPubMed
Twinn, D, Hjort, L, Novakovic, B, Ozanne, S, Saffery, R. Intrauterine programming of obesity and type 2 diabetes. Diabetologia. 2019; 62, 1789–1801. https://doi.org/10.1007/s00125-019-4951-9 CrossRefGoogle Scholar
Ouni, M, Schürmann, A. Epigenetic contribution to obesity. Diabetologia. 2020; 62, 134–145. https://doi.org/10.1007/s00125-019-4951-9 Google Scholar
Ferraro, Z, Adamo, KB. Pediatric obesity: it’s time for prevention before conception can maternal obesity program pediatric obesity? Clin Med Ped. 2008; 2. CMPed. S1099.Google Scholar
Smith, J, Cianflone, K, Biron, S, et al. Effects of maternal surgical weight loss in mothers on intergenerational transmission of obesity. J Clin Endocrinol Metal. 2009; 94, 4275–4283.CrossRefGoogle ScholarPubMed
Barraco, G, Luciano, R, Semeraro, M, Prieto-Hontoria, P, Manco, M. Recently discovered adipokines and cardio-metabolic comorbidities in childhood obesity. Int J Mol Sci. 2014; 15, 19760–19776. https://doi.org/10.1007/s00335-020-09835-3 CrossRefGoogle ScholarPubMed
Manco, M, Putignani, L, Bottazzo, GF. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev. 2010; 31, 817–844.CrossRefGoogle ScholarPubMed
Niklowitz, P, Rothermel, J, Lass, N, Barth, A, Reinehr, T. Link between chemerin, central obesity, and parameters of the Metabolic Syndrome: findings from a longitudinal study in obese children participating in a lifestyle intervention. Int J Obes. 2018; 42, 1743–1752. https://doi.org/10.1038/s41366-018-0157-3 CrossRefGoogle Scholar
El-Deeb, TS, Bakkar, SM, Eltoony, L, et al. The adipokine chemerin and fetuin-A serum levels in type 2 diabetes mellitus: relation to obesity and inflammatory markers. Egypt J Immunol. 2018; 25, 191–202.Google ScholarPubMed
Ernst, MC, Sinal, CJ. Chemerin: at the crossroads of inflammation and obesity. Trends Endocrinol Metab. 2010; 21, 660–667. https://doi.org/10.1016/j.tem.2010.08.001.CrossRefGoogle Scholar
Mazaki-Tovi, S, Kasher-Meron, M, Hemi, R, et al. Chemerin is present in human cord blood and is positively correlated with birthweight. Am J Obstet and Gynacol. 2012; 207, 412. e1–412. e10.CrossRefGoogle ScholarPubMed
Garces, M, Sanchez, E, Acosta, B, et al. Expression and regulation of chemerin during rat pregnancy. Placenta. 2012; 33, 373–378.CrossRefGoogle ScholarPubMed
Kasher-Meron, M, Mazaki-Tovi, S, Barhod, E, et al. Chemerin concentrations in maternal and fetal compartments: implications for metabolic adaptations to normal human pregnancy. J Perinat Med. 2014; 42, 371–378. https://doi.org/10.1515/jpm-2013-0166.CrossRefGoogle ScholarPubMed
Gillman, MW, Rifas-Shiman, S, Berkey, CS, Field, AE, Colditz, GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 2003; 111, e221–e6.CrossRefGoogle ScholarPubMed
Eriksson, JG, Venojärvi, M, Osmond, C. Prenatal and childhood growth, chemerin concentrations, and metabolic health in adult life. Int J Endocrinol. 2016; 2016, 3838646. https://doi.org/10.1155/2016/3838646.CrossRefGoogle ScholarPubMed
Brunetti, L, Orlando, G, Ferrante, C, et al. Peripheral chemerin administration modulates hypothalamic control of feeding. Peptides. 2014; 51, 115–121.CrossRefGoogle ScholarPubMed
Helfer, G, Ross, AW, Thomson, LM, et al. A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance. Sci Rep. 2016; 6, 26830. https://doi.org/10.1038/srep26830.CrossRefGoogle ScholarPubMed
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