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Journal of the Society for Gynecologic Investigation
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Maternal Interleukin-6: Marker of Fetal Growth and Adiposity

Tatjana Radaelli, MD

Jennifer Uvena-Celebrezze, MD

Judi Minium

Larraine Huston-Presley

Patrick Catalano, MD

Case Western, Cleveland, OH

Sylvie Hauguel-de Mouzon, PhD

Reproductive Biology, OBGYN, Case Western, 2500 Metrohealth Dr., Cleveland, OH 44109 shdemouzon{at}metrohealth.org

Fetal overgrowth and higher adiposity are hallmarks of pregnancy with maternal obesity and poor glucose tolerance, two conditions associated with decreased maternal insulin sensitivity. In non-pregnant individuals, adipokines, vasoactive peptides, and components of the immune system crosstalk with metabolic factors to generate signals triggering obesity and impaired insulin action. We have investigated circulating maternal and fetal cytokines and growth-factors as potential biochemical markers of fetal adiposity. Mothers and neonates were classified into three tertiles (T1-T3) using total neonatal fat mass as the outcome with 309 ± 25 g in T1, 478 ± 40 g in T2, and 529 ± 39 g in T3. Umbilical cord endothelin-1 (ET-1), C-peptide, and leptin were higher in T3 and T2 versus T1. Only cord leptin was strongly associated with fetal fat mass (P < .01), whereas neonatal lean body mass was negatively correlated with maternal insulin-like growth factor binding protein-I (IGFBP-I) (r = -0.53, P < .04). This study shows an association between increased fetal adiposity and maternal systemic interleukin-6 (IL-6). No such correlation was found with factors circulating in cord blood, suggesting that the stimuli favoring fetal fat accretion derive from maternal or placental sources rather than from the fetus.

Key Words: Fetal adiposity • cytokines • growth factors • obesity • pregnancy

References

  • 1. Hales CN, Barker DJP. The thrifty phenotype hypothesis. Br Med Bull 2001;60:5-20.[Abstract/Free Full Text]
  • 2. Ogden CL, Flegal KM, Carroll MD, et al. Prevalence and trends in overweight among US children and adolescents 1999-2000. JAMA 2002;228:1728-1732.
  • 3. Catalano PM, Thomas A, Huston-Presley L, et al. Increased fetal adiposity: A very sensitive marker of abnormal in utero development. Am J Obstet Gynecol 2003;189:1698-1704.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 4. Pettitt DJ, Jovanovic L. Birth weight as a predictor of type 2 diabetes mellitus: The U shaped curve. Curr Diab Rep 2001;1:78-81.[Medline] [Order article via Infotrieve]
  • 5. Manderson JG, Mullan B, Patterson CC, et al. Cardiovascular and metabolic abnormalities in the offpsring of diabetic pregnancy. Diabetologia 2002;45:991-996.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 6. Sparks JW. Human intrauterine growth and nutrient accretion. Semin Perinatol 1984;8:74-93.[Web of Science][Medline] [Order article via Infotrieve]
  • 7. Catalano PM, Drago NMAmini SB. Maternal carbohydrate metabolism and its relationship to fetal growth and body composition. Am J Obstet Gynecol 1995;172:1464-1470.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 8. Boyne MS, Thame M, Bennet FI, et al. The relationship among circulating insulin-like growth factor (IGF)-1, IGF-Binding proteins-1 and -2, and birth anthropometry: A prospective study. J Clin Endocrinol Metab 2003;88:1687-1691.[Abstract/Free Full Text]
  • 9. Maachi M, Pieroni L, Bruckert E, et al. Systemic low-grade inflammation is related to both circulating and adipose tissue TNF-a, leptin and IL-6 levels in obese women. Int J Obesity 2004;28:993-997.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 10. Ramsay JE, Ferrell WR, Crawford L, et al. Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways. J Clin Endocrinol Metab 2002;87:4231-4237.[Abstract/Free Full Text]
  • 11. Guerre-Millo M. Adipose tissue and adipokines: For better or worse. Diabetes Metab 2004;30:13-19.[Web of Science][Medline] [Order article via Infotrieve]
  • 12. Radaelli T, Varastehpour A, Catalano P, et al. Gestational diabetes induces placental genes for chronic stress and inflammatory pathways. Diabetes 2003;52:2951-2958.[Abstract/Free Full Text]
  • 13. Coughlan MT, Oliva K, Georgiou HM, Permezel JM, Rice GE. Glucose-induced release of tumour necrosis factor-alpha from human placental and adipose tissues in gestational diabetes mellitus. Diabet Med 2001;18:921-927.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 14. Catalano PM, Thomas AJ, Avallone DA, et al. Anthropometric estimation of neonatal body composition. Am J Obstet Gynecol 1995;173:1176-1181.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 15. Carpenter M, Coustan D. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982;144:768-773.[Web of Science][Medline] [Order article via Infotrieve]
  • 16. Retnakaran R, Hanley AJ, Raif N, et al. C-reactive protein and gestational diabetes: The central role of maternal obesity. J Clin Endocrinol Metab 2003;88:3507-3512.[Abstract/Free Full Text]
  • 17. Kern PA, Ranganathan S, Li C, et al. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001;280:E745-E751.[Abstract/Free Full Text]
  • 18. Lepercq J, Caüzac M, Lahlou N, et al. Overexpression of placental leptin in diabetic pregnancies: A critical role for insulin. Diabetes 1998;47:847-850.[Abstract]
  • 19. Kirwan JP, Hauguel-de Mouzon S, Lepercq, J, et al. TNF{alpha} is a predictor of insulin resistance in human pregnancy. Diabetes 2002;51:2207-2213.[Abstract/Free Full Text]
  • 20. Arner P. The adipocyte in insulin resistance: Key molecules and the impact of thiazolidinediones. Trends Endocrinol Metab 2003;14:137-145.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 21. Dahhgren J, Nilsson C, Jennische E, et al. Prenatal cytokine exposure results in obesity and gender-specific programming. Am J Physiol Endocrinol Metab 2001;281:E326-E334.[Abstract/Free Full Text]
  • 22. Ozcan U, Cao Q, Yilmaz E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004;306:457-461.[Abstract/Free Full Text]
  • 23. Mather KJ, Mirzamohammadi B, Lteif A, et al. Endothelin contributes to basal vascular tone and endothelil dysfunction in human obesity and type 2 diabetes. Diabetes 2002;51:3517-3523.[Abstract/Free Full Text]
  • 24. Wilkes JJ, Hevener A, Olefsky J. Chronic endothelin-1 treatment leads to insulin resistance in vivo. Diabetes 2003;52:1904-1909.[Abstract/Free Full Text]
  • 25. Fant ME, Nanu L, Word RA. A potential role for endothelin-1 in human placental growth: Interactions with the insulin-like growth factor family of peptides. J Clin Endocrinol Metab 1992;74:1158-1163.[Abstract]
  • 26. Lepercq J, Taupin P, Dubois-Laforgue D, et al. Heterogeneity of fetal growth in type 1 diabetic pregnancy. Diabetes Metab 2001;3:339-344.
  • 27. Okereke NC, Uvena-Celebrezze J, Huston-Presley L, et al. The effect of gender and gestational diabetes mellitus on cord leptin concentration. Am J Obstet Gynecol 2002;187:798-803.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 28. Lepercq J, Challier JC, Guerre-Millo M, et al. Placental leptin production, evidence that fetal adipose tissue produces leptin. J Clin Endocrinol Metab 2001;86:2409-2413.[Abstract/Free Full Text]
  • 29. Leroy P, Dessolin S, Villageosi P, et al. Expressionof ob gene in adipose cells. Regulation by insulin. Biol Chem 1996;271:2365-2368.
  • 30. Susa JB, Widness JA, Hintz R, Liu F, Sehgal P, Schwartz R. Somatomedins and insulin in diabetic pregnancies: Effects on fetal macrosomia in the human and rhesus monkey. J Clin Endocrinol Metab 1984;6:1099-1105.
  • 31. Schwartz R, Gruppuso PA, Petzold K, Brambilla D, Hiilesmaa V, Teramo KA. Hyperinsulinemia and macrosomia in the fetus of the diabetic mother. Diabetes Care 1994;7:640-648.
  • 32. Dornhorst A, Nicholls JS, Ali K, et al. Fetal proinsulin and birthweight. Diab Med 1994;11:177-181.[Web of Science][Medline] [Order article via Infotrieve]
  • 33. Ong K, Kratzsch J, Kiess W, et al. Size at birth and cord blood levels of insulin, insulinlike growth factors I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-3 and the soluble IGF-II/Mannose-6-phosphate receptor in term human infants. J Clin Endocinol Metab 2000;85:4266-4269.[Abstract/Free Full Text]
  • 34. Giudice LC, de Zegher F, Gargosky SE, et al. Insulin-like growth factors and their binding proteins in the term and preterm human fetus and neonate with normal and extremes of intrauterine growth. J Clin Endocrinol Metab 1995;80:1548-1555.[Abstract/Free Full Text]
  • 35. Delmis J, Drazancic A, Ivanisevic M, et al. Glucose, insulin HGH and IGF-I levels in maternal serum, amniotic fluid and umbilical venous serum: A comparison between late normal pregnancy and pregnancies complicated with diabetes and fetal growth retardation. J Perinat Med 1992;20:47-56.[Web of Science][Medline] [Order article via Infotrieve]
  • 36. Baker J, Liu JP, Robertson EJ, et al. Role of insulin-like growth factors in embryonic and post natal growth. Cell 1993;75:73-82.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 37. Kniss DA, Shubert PJ, Zimmerman PD, et al. Insulin-like growth factors. Their regulation of glucose and amino acid transport in placental trophoblasts isolated from first-tgrimester chorionic villi. J Reprod Med 1994;39:249-256.[Web of Science][Medline] [Order article via Infotrieve]

Journal of the Society for Gynecologic Investigation, Vol. 13, No. 1, 53-57 (2006)
DOI: 10.1016/j.jsgi.2005.10.003
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