The Importance of the Adiponectin and Leptin Relationship in In Utero and Infant Growth



Adiponectin is an adipocyte-derived, insulin-sensitizing, and anti-inflammatory cytokine that circulates in concentrations a thousand-fold greater than those of leptin or insulin. Leptin is a fat cell derived, 16 kDa protein that acts centrally to signal long-term energy stores to the brain and induces satiety by stimulating anorexigenic and inhibiting orexigenic neuropeptides. Adiponectin is measurable in cord serum by the 24th week of gestation, and concentrations rise 20-fold to term. Cord blood adiponectin values are significantly higher than those found in children and adults, in whom concentrations are inversely related to fat mass and body mass index, and, in contrast, correlate positively to birth weight, body mass index, and weight to length ratio. Umbilical cord leptin correlates positively with birth weight across the spectrum of fetal growth patterns. While placenta can secrete adiponectin, most of the adipokine appears to originate from fetal brown adipose tissue that forms by 14 weeks gestation. High molecular weight adiponectin, the presumed active isoform, correlates with leptin concentrations in cord blood. Lower leptin values in cord blood from small for gestational age babies may play a role in programming catch-up growth during infancy, while low levels of adiponectin in small for gestational age infants may contribute to childhood obesity and insulin resistance. The ratio of total adiponectin to leptin has been shown to correlate positively with weight gain from birth to mid-infancy.


Adiponectin Concentration Total Adiponectin High Molecular Weight Adiponectin Birth Weight Standard Deviation Score Fetal Growth Pattern 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Adiponectin receptor 1


Appropriate for gestational age


Agouti-related protein

AMP kinase

5-adenosine monophosphate-activated protein kinase


Brown adipose tissue


Body mass index


Cocaine and amphetamine-related transcript


Dual-energy X-ray absorptiometry


Extracellularly regulated kinase 1/2




High molecular weight




Insulin-like growth factor 1


Interleukin-1 beta




Intrauterine growth retardation


Janus kinase-signal transducers and activator of transcription


Large for gestational age


Low molecular weight




Mitogen-activated protein kinase


Nuclear factor kappa beta


Neuropeptide Y


Online Mendelian Inheritance in Man


Plasminogen activator inhibitor


Prostaglandin E2 alpha




Peroxisomal proliferators-activated receptor-gamma


Standard deviation


Standard deviation score


Standard error of the mean


Small for gestational age


Tissue necrosis factor-alpha


White adipose tissue


  1. Araki S, Dobashi K, Kubo K, Asayama K, Shirahata A. High molecular weight, rather than total, adiponectin levels better reflect metabolic abnormalities associated with childhood obesity. J Clin Endocrinol Metab. 2006;91:5113–6.PubMedCrossRefGoogle Scholar
  2. Blum WF, Englaro P, Hanitsch S, Juul A, Hertel NT, Müller J, Skakkebæk NE, Heiman ML, Birkett M, Attanasio AM, Keiss W, Rascher W. Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J Clin Endocrinol Metab. 1997;82:2904–10.PubMedCrossRefGoogle Scholar
  3. Bouret SG, Draper SJ, Simerly RB. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science. 2004;304:108–10.PubMedCrossRefGoogle Scholar
  4. Bronsky J, Karpisek M, Bronska E, Pechova M, Jancikova B, Kotolova H, Stejskal D, Prusa R, Nevoral J. Nevoral Adiponectin, adipocyte fatty acid binding protein, and epidermal fatty acid binding protein: proteins newly identified in human breast milk. Clin Chem. 2006;52:1763–70.PubMedCrossRefGoogle Scholar
  5. Chen J, Tan B, Karteris E, Zervou S, Digby J, Hillhouse EW, Vatish M, Randeva HS. Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia. 2006;49:1292–302.PubMedCrossRefGoogle Scholar
  6. Chiesa C. Ghrelin, leptin, IGF-1, ICiFBP-3, and insulin concentrations at birth: is there a relationship with fetal growth and neonatal anthropometry? Clin Chem. 2008;54(3):550–8.PubMedCrossRefGoogle Scholar
  7. Diamond F, Dharamraj C, Luther S, Eichler D. The leptin/adiponectin ratio in mid-infancy correlates with weight gain in healthy term infants, but is unrelated to serum insulin concentrations, body mass index, or skin fold thickness. J Pediatr Endocrinol Metab. 2008;21:1133–8.CrossRefGoogle Scholar
  8. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;190:197–207.CrossRefGoogle Scholar
  9. Dundar NO, Anal Ozden, Dundar B, Ozkan H, Caliskan S, Büyükgebiz A. Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants. J Pediatr Endocrinol Metab. 2005;18:181–7.PubMedCrossRefGoogle Scholar
  10. Dunger D, Ong K. Abundance of adiponectin in the newborn. Clin Endocrinol. 2004;61:416–7.CrossRefGoogle Scholar
  11. Elefteriou F, Takeda S, Ebihara K, Magre J, Patano N, Kim CA, Ogawa Y, Liu X, Ware SM, Craigen WJ, Robert JJ, Nakao K, Capeau J, Karsenty G. Serum leptin level is a regulator of bone mass. Proc Natl Acad Sci USA. 2004;101:3258–63.PubMedCrossRefGoogle Scholar
  12. Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, Paschke R. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L I adipocytes. Biochem Biophys Res Commun. 2003;301:1045–50.PubMedCrossRefGoogle Scholar
  13. Gohlke BC, Bartmann P, Fimmers R, Huber A, Hecher K, Roth CL. Fetal adiponectin and resistin in correlation with birth weight difference in monozygotic twins with discordant growth. Horm Res. 2008;69:37–44.PubMedCrossRefGoogle Scholar
  14. Grosfeld A, Andre J, Hauguel-de Mouzon S, Berra E, Pouyssegur J, Guerre-Millo M. Hypoxia-inducible factor 1 transactivates the human leptin gene promoter. J Biol Chem. 2002;277:42953–7.PubMedCrossRefGoogle Scholar
  15. Hara K, Horikoshi M, Yamauchi T, Yago H, Miyazaki O, Ebinuma H, Imai Y, Nagai R, Kadowaki T. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care. 2006;29:1357–2.PubMedCrossRefGoogle Scholar
  16. Harigaya A. Relationship between concentration of serum leptin and fetal growth. J Clin Endocrinol Metab. 1997;82(10):3281–4.PubMedCrossRefGoogle Scholar
  17. Hytinantti T, Koistinen HA, Koivisto VA, Karonen S-L, Andersson S. Changes in leptin concentration during the early postnatal period: adjustment to extrauterine life? Pediatr Res. 1999;45(2):197–201.PubMedCrossRefGoogle Scholar
  18. Ibañez L, Sebastiani G, Lopez-Bermejo A, Diaz M, Gomez-Roing MD, de Zegher F. Gender specificity of body adiposity and circulating adiponectin, visfatin, instil and insulin growth factor-I at term birth: relation to prenatal growth. J Clin Endocrinol Metab. 2008;93:2774–8.PubMedCrossRefGoogle Scholar
  19. Iniguez G, Soto N, Avila A, Salazar T, Ong K, Duner D, Mericq VJ. Adiponectin levels in the first two years of life in a prospective cohort: relations with weight gain, leptin levels and insulin sensitivity. J Clin Endocrinol Metab. 2004;89:5500–3.PubMedCrossRefGoogle Scholar
  20. Inoue M, Itabashi K, Nakano Y, Nakano Y, Tobe T. High-molecular-weight adiponectin and leptin levels in cord blood are associated with anthropometric measurements at birth. Horm Res. 2008;70:268–72.PubMedCrossRefGoogle Scholar
  21. James RJ, James A, Drewett RF, Cheetham TD. Milk intake and feeding behavior in the first week of life and its relationship to cord blood ghrelin, leptin, and insulin concentrations. Pediatr Res. 2007;62:695–9.PubMedCrossRefGoogle Scholar
  22. Jaquet D. Ontogeny of leptin in human fetuses and newborns: effect of intrauterine growth retardation of serum leptin concentrations. J Clin Endocrinol Metab. 1998;83(4):1243–6.PubMedCrossRefGoogle Scholar
  23. Jenkins LD. Maternal leptin concentrations are similar in African Americans and Caucasians in normal pregnancy, preeclampsia and small-for-gestational-age infants. Hypertens Pregnancy. 2007;26:101–9.PubMedCrossRefGoogle Scholar
  24. Kajantie E, Hytinantti T, Hovi P, Andersson S. Cord plasma adiponectin: a 20-fold rise between 24 weeks gestation and term. J Clin Endocrinol Metab. 2004;89:4031–6.PubMedCrossRefGoogle Scholar
  25. Kayemba-Kay S. Gender, smoking during pregnancy and gestational age influence cord leptin concentrations in newborn infants. Eur J Endocrinol. 2008;159:217–4.CrossRefGoogle Scholar
  26. Koo WWK, Hammami M, Hockman EM. Developmental variations in plasma leptin, leptin soluble receptor and their molar ratio in healthy infants. Nutr J. 2007;6:11.PubMedCrossRefGoogle Scholar
  27. Koistinen H. Leptin concentration in cord blood correlates with intrauterine growth. J Clin Endocrinol Metab. 1997;82(10):3328–30.PubMedCrossRefGoogle Scholar
  28. Koklu E. Aortic intima-media thickness, serum IGF-1, IGH3P-3, and leptin levels in intrauterine growth-restricted newborns of healthy mothers. Pediatr Rsch. 2007;62(6):704–9.CrossRefGoogle Scholar
  29. Kyriakakou M. Leptin and deiponectin concentrations in intrauterine growth restricted and appropriate for gestational age fetuses, neonates, and their mothers. Eur J Endocrinol. 2008;158:343–8.PubMedCrossRefGoogle Scholar
  30. Lappas M, Permezel M, Rice GE. Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase 1/2. Endocrinology. 2005;146:3334–42.PubMedCrossRefGoogle Scholar
  31. Mantzoros CS, Rifas-Shiman R, Williams CJ, Fargnoli JL, Kelesidis T, Gillman MW. Cord blood leptin and adiponectin as predictors of adiposity in children at 3 years of age: a prospective cohort study. Pediatrics. 2009;123:682–9.PubMedCrossRefGoogle Scholar
  32. Martínez-Cordero C, Amador-Licona N, Guízar-Mendoza JM, Hernández-Méndez J, Ruelas-Orozco G. Body fat at birth and cord blood levels of insulin, adiponectin, leptin, and insulin-like growth factor-1 in small-for-gestational-age infants. Arch Med Res. 2006;37:490–4.PubMedCrossRefGoogle Scholar
  33. Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H, Nishimura H, Yoshimasa Y, Tanaka I, Mori T, Nakao K. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med. 1997;3:1029–33.PubMedCrossRefGoogle Scholar
  34. Matsuda J. Serum leptin concentration in cord blood: relationship to birth weight and gender. J Clin Endocrinol Metab. 1997;82(5):1642–4.PubMedCrossRefGoogle Scholar
  35. Matsuda J, Yokota I, Iida M, Murakami T, Yamada M, Saijo T, Naito E, Ito M, Shima K, Kuroda Y. Dynamic changes in serum leptin concentrations during the fetal and neonatal periods. Pediatr Res. 1999;45(1):71–5.PubMedCrossRefGoogle Scholar
  36. Mazaki-Tovi S. Adiponectin and leptin concentrations in dichorionic twin with discordant and concordant growth. J Clin Endocrinol Metab. 2009;94:892–8.PubMedCrossRefGoogle Scholar
  37. Mazaki-Tovi S, Kanety H, Pariente C, Hemi R, Schiff E, Sivan E. Cord blood adiponectin in large-for-gestational-age newborns. Am J Obstet Gynecol. 2005;193:1238–42.PubMedCrossRefGoogle Scholar
  38. Mazaki-Tovi S, Kanety H, Pariente C, Hemi R, Yinon Y, Wiser A, Schiff E, Sivan E. Adiponectin and leptin concentrations in dichorionic twins with discordant and concordant growth. J Clin Endocrinol Metab. 2009;94:892–8.PubMedCrossRefGoogle Scholar
  39. Mistry, A, Swick A, Romsos D. Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice. Am J Physiol. 1999;277:R742–7.PubMedGoogle Scholar
  40. Pighetti M. Maternal serum and umbilical cord blood leptin concentrations with fetal growth restriction. Obstet Gynecol. 2003;102:535–43.PubMedCrossRefGoogle Scholar
  41. Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X, Friedman JM, Horvath TL. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science. 2004;304:110–5.PubMedCrossRefGoogle Scholar
  42. Savino F, Liguori SA, Fissore MF, Palumeri E, Calabrese R, Oggero R, Silvestro L, Miniero R. Looking for a relation between serum leptin concentration and body composition parameters in healthy term infants in the first 6 month of life. J Pediatr Gastroenterol Nutr. 2008;46:348–51.PubMedCrossRefGoogle Scholar
  43. Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL. Leptin reverses insulin resistance and diabetes mellitus in mice with congential lipodystrophy. Nature. 1999;401:73–6.PubMedCrossRefGoogle Scholar
  44. Sivan E, Mazaki-Tovi S, Pariente C, Efraty Y, Schiff E, Hemi R, Kanety H. Adiponectin in human cord blood: relation to fetal birth weight and gender. J Clin Endocrinol Metab. 2003;88:5656–60.PubMedCrossRefGoogle Scholar
  45. Struwe E, Berzi GM, Schild RL, Dötsch J. Gene expression of placental hormones regulating energy balance in small for gestational age neonates. Eur J Obstet Gynecol Reprod Biol. 2009;142:38–42.PubMedCrossRefGoogle Scholar
  46. Takaya J. Intracellular magnesium and adipokines in umbilical cord plasma and infant birth size. Pediatr Res. 2007;62:700–3.PubMedCrossRefGoogle Scholar
  47. Vickers MH, Gluckman PD, Coveny AH, Hofman PL, Cutfield WS, Gertler A, Breier BH, Harris M. Neonatal leptin treatment reverses developmental programming. Endocrinology. 2005;146:4211–6.PubMedCrossRefGoogle Scholar
  48. Weyermann M, Beermann C, Brenner H, Rothenbacher D. Adiponectin and leptin in maternal serum, cord blood, and breast milk. Clin Chem. 2006;52:2095–102.PubMedCrossRefGoogle Scholar
  49. Wiznitzer A. Cord leptin level and fetal macrosomia. Obstet Gynecol. 2000;96:707–13.PubMedCrossRefGoogle Scholar
  50. Woo JG, Guerrero ML, Altaye M, Ruiz-Palacios GM, Martin LJ, Dubert-Ferrandon A, Newburg DS, Morrow AL. Human milk adiponectin is associated with infant growth in two independent cohorts. Breastfeed Med. 2009;4:101–9.PubMedCrossRefGoogle Scholar
  51. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423:762–9.PubMedCrossRefGoogle Scholar
  52. Yura S, Itoh H, Sagawa N, Yamamoto H, Masuzaki H, Nakao K, Kawamura M, Takemura M, Kakui K, Ogawa Y, Fujii S. Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell Metab. 2005;1:371–8.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Pediatric EndocrinologyDiabetes and Metabolism, All Children’s Hospital, University of South Florida College of MedicineTampaUSA
  2. 2.Division of Pediatric EndocrinologyDiabetes and Metabolism, University of South Florida College of MedicineTampaUSA
  3. 3.All Children’s HospitalSt. PetersburgUSA

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