Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Physiology

Longitudinal changes in adipokines and free leptin index during and after pregnancy in women with obesity

International Journal of Obesity volume 44, pages 675–683 (2020)Cite this article

Subjects

Abstract

Objective

Detailed data on adipokines and body composition during and after pregnancy in women of different BMI categories are lacking. Furthermore, adipokine regulation during pregnancy and the factors contributing to gestational insulin resistance are not completely understood. The objective was to longitudinally determine adipokine levels, body composition, and insulin sensitivity during and after pregnancy in women of healthy weight (HW) and with obesity (OB), and identify factors associated with insulin resistance.

Design

Women (30 HW, 19 OB) underwent blood sampling and body composition examination, by air-displacement plethysmography, longitudinally during pregnancy (trimesters 1, 2, 3) and after pregnancy (6, 12, 18 months postpartum). Serum leptin, soluble leptin receptor (sOB-R), and adiponectin levels were measured and free leptin index (FLI) and homeostatic model assessment of insulin resistance (HOMA-IR) determined.

Results

Fat mass and leptin increased during pregnancy in the HW (p < 0.01) but not in the OB group. sOB-R increased during pregnancy in both groups (p < 0.001). Thus, FLI was unchanged in HW throughout pregnancy but reduced in OB (p = 0.001), although consistently higher in OB. Adiponectin decreased in both groups during pregnancy (p < 0.001 for HW, p = 0.01 for OB). After pregnancy, adiponectin increased in both groups, but more markedly in OB where it reached trimester 1 levels. Multivariable regression identified FLI as the variable most strongly associated with HOMA-IR in all trimesters, but not after pregnancy.

Conclusions

Leptin, sOB-R, adiponectin, and FLI undergo marked changes during and after pregnancy with differences in women of different BMI. We suggest that leptin activity is regulated by its soluble receptor and that this is an important factor for optimizing fat mass and insulin sensitivity during pregnancy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Linne Y. Effects of obesity on women’s reproduction and complications during pregnancy. Obesity Rev. 2004;5:137–43.

    CAS  Google Scholar 

  2. Cedergren M. Effects of gestational weight gain and body mass index on obstetric outcome in Sweden. Int J Gynaecol Obstet. 2006;93:269–74.

    CAS  PubMed  Google Scholar 

  3. Gunderson E, Abrams B, Selvin S. Does the pattern of postpartum weight change differ according to pregravid body size? Int J Obes Relat Metab Disord. 2001;25:853–62.

    CAS  PubMed  Google Scholar 

  4. Briana DD, Malamitsi-Puchner A. Reviews: adipocytokines in normal and complicated pregnancies. Reprod Sci. 2009;16:921–37.

    CAS  PubMed  Google Scholar 

  5. Park H-K, Ahima RS. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism. 2015;64:24–34.

    CAS  PubMed  Google Scholar 

  6. Tessier D, Ferraro Z, Gruslin A. Role of leptin in pregnancy: consequences of maternal obesity. Placenta. 2013;34:205–11.

    CAS  PubMed  Google Scholar 

  7. Ladyman S, Augustine R, Grattan D. Hormone interactions regulating energy balance during pregnancy. J Neuroendocrinol. 2010;22:805–17.

    CAS  PubMed  Google Scholar 

  8. Chan JL, Blüher S, Yiannakouris N, Suchard MA, Kratzsch J, Mantzoros CS. Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin: observational and interventional studies in humans. Diabetes. 2002;51:2105–12.

    CAS  PubMed  Google Scholar 

  9. Ingelsson E, Larson MG, Yin X, Wang TJ, Meigs JB, Lipinska I, et al. Circulating ghrelin, leptin, and soluble leptin receptor concentrations and cardiometabolic risk factors in a community-based sample. J Clin Endocrinol Metab. 2008;93:3149–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Page-Wilson G, Reitman-Ivashkov E, Meece K, White A, Rosenbaum M, Smiley R, et al. Cerebrospinal fluid levels of leptin, proopiomelanocortin, and agouti-related protein in human pregnancy: evidence for leptin resistance. J Clin Endocrinol Metab. 2013;98:264–71.

    CAS  PubMed  Google Scholar 

  11. Andersson-Hall U, Svedin P, Andreasson U, Gren M, Ingemansson A, Zetterberg H, et al. Central and peripheral leptin and agouti-related protein during and after pregnancy in relation to weight change. Clin Endocrinol. 2018;88:263–71.

    CAS  Google Scholar 

  12. Nuamah MA, Sagawa N, Yura S, Mise H, Itoh H, Ogawa Y, et al. Free-to-total leptin ratio in maternal plasma is constant throughout human pregnancy. Endocr J. 2003;50:421–8.

    CAS  PubMed  Google Scholar 

  13. Lewandowski K, Horn R, O’Callaghan C, Dunlop D, Medley G, O’Hare P, et al. Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic pregnancies. J Clin Endocrinol Metab. 1999;84:300–6.

    CAS  PubMed  Google Scholar 

  14. Sommer C, Gulseth HL, Jenum AK, Sletner L, Thorsby PM, Birkeland KI. Soluble leptin receptor and risk of gestational diabetes in a multiethnic population: a prospective cohort study. J Clin Endocrinol Metab. 2016;101:4070–5.

    CAS  PubMed  Google Scholar 

  15. Hinkle SN, Rawal S, Liu D, Chen J, Tsai MY, Zhang C. Maternal adipokines longitudinally measured across pregnancy and their associations with neonatal size, length, and adiposity. Int J Obes. 2019;43:1422–34.

    CAS  Google Scholar 

  16. Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metabolism. 2002;13:84–89.

    CAS  Google Scholar 

  17. Aye IL, Powell TL, Jansson T. Review: Adiponectin–the missing link between maternal adiposity, placental transport and fetal growth? Placenta. 2013;34:S40–S45.

    CAS  PubMed  Google Scholar 

  18. Hendler I, Blackwell SC, Mehta SH, Whitty JE, Russell E, Sorokin Y, et al. The levels of leptin, adiponectin, and resistin in normal weight, overweight, and obese pregnant women with and without preeclampsia. Am J Obstet Gynecol 2005;193:979–83.

    CAS  PubMed  Google Scholar 

  19. Lekva T, Roland MCP, Michelsen AE, Friis CM, Aukrust P, Bollerslev J, et al. Large reduction in adiponectin during pregnancy is associated with large-for-gestational-age newborns. J Clin Endocrinol Metab. 2017;102:2552–9.

    PubMed  Google Scholar 

  20. Chen C, Xu X, Yan Y. Estimated global overweight and obesity burden in pregnant women based on panel data model. PLoS ONE. 2018;13:e0202183.

    PubMed  PubMed Central  Google Scholar 

  21. Bosaeus M, Hussain A, Karlsson T, Andersson L, Hulthen L, Svelander C, et al. A randomized longitudinal dietary intervention study during pregnancy: effects on fish intake, phospholipids, and body composition. Nutr J. 2015;14:1.

    PubMed  PubMed Central  Google Scholar 

  22. Svensson H, Wetterling L, Bosaeus M, Oden B, Oden A, Jennische E, et al. Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance. Int J Obes. 2016;40:646–53.

    CAS  Google Scholar 

  23. Van Raaij J, Peek M, Vermaat-Miedema SH, Schonk CM, Hautvast J. New equations for estimating body fat mass in pregnancy from body density or total body water. Am J Clin Nutr. 1988;48:24–29.

    PubMed  Google Scholar 

  24. Hopkinson JM, Butte NF, Ellis KJ, Wong WW, Puyau MR, Smith E. Body fat estimation in late pregnancy and early postpartum: comparison of two-, three-, and four-component models. Am J Clin Nutr. 1997;65:432–8.

    CAS  PubMed  Google Scholar 

  25. National Research Council. Weight gain during pregnancy: reexamining the guidelines. Washington, DC: National Academies Press; 2010.

  26. Kratzsch J, Lammert A, Bottner A, Seidel B, Mueller G, Thiery J, et al. Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence. J Clin Endocrinol Metab. 2002;87:4587–94.

    CAS  PubMed  Google Scholar 

  27. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27:1487–95.

    PubMed  Google Scholar 

  28. Schaab M, Kratzsch J. The soluble leptin receptor. Best Pract Res Clin Endocrinol Metab. 2015;29:661–70.

    CAS  PubMed  Google Scholar 

  29. Tu H, Kastin AJ, Hsuchou H, Pan W. Soluble receptor inhibits leptin transport. J Cell Physiol. 2008;214:301–5.

    CAS  PubMed  Google Scholar 

  30. van Dielen FM, van ‘t Veer C, Buurman WA, Greve JW. Leptin and soluble leptin receptor levels in obese and weight-losing individuals. J Clin Endocrinol Metab. 2002;87:1708–16.

    PubMed  Google Scholar 

  31. Gavrilova O, Barr V, Marcus-Samuels B, Reitman M. Hyperleptinemia of pregnancy associated with the appearance of a circulating form of the leptin receptor. J Biol Chem. 1997;272:30546–51.

    CAS  PubMed  Google Scholar 

  32. Farley D, Choi J, Dudley D, Li C, Jenkins S, Myatt L, et al. Placental amino acid transport and placental leptin resistance in pregnancies complicated by maternal obesity. Placenta. 2010;31:718–24.

    CAS  PubMed  Google Scholar 

  33. Mørkrid K, Jenum AK, Sletner L, Vårdal MH, Waage CW, Nakstad B, et al. Failure to increase insulin secretory capacity during pregnancy-induced insulin resistance is associated with ethnicity and gestational diabetes. Eur J Endocrinol. 2012;167:579–88.

    PubMed  Google Scholar 

  34. Vinter C, Jørgensen J, Ovesen P, Beck‐Nielsen H, Skytthe A, Jensen D. Metabolic effects of lifestyle intervention in obese pregnant women. Results from the randomized controlled trial ‘Lifestyle in Pregnancy’(LiP). Diabet Med. 2014;31:1323–30.

    CAS  PubMed  Google Scholar 

  35. Sun Q, van Dam RM, Meigs JB, Franco OH, Mantzoros CS, Hu FB. Leptin and soluble leptin receptor levels in plasma and risk of type 2 diabetes in US women: a prospective study. Diabetes. 2010;59:611–8.

    CAS  PubMed  Google Scholar 

  36. Sommer C, Lee S, Gulseth HL, Jensen J, Drevon CA, Birkeland KI. Soluble leptin receptor predicts insulin sensitivity and correlates with upregulation of metabolic pathways in men. J Clin Endocrinol Metab. 2017;103:1024–32.

    Google Scholar 

  37. Chen D, Xia G, Xu P, Dong M. Peripartum serum leptin and soluble leptin receptor levels in women with gestational diabetes. Acta Obst et Gynecol Scand. 2010;89:1595–9.

    CAS  Google Scholar 

  38. Krizova J, Eretova V, Haluzikova D, Anderlova K, Housova J, Kotrlikova E, et al. Soluble leptin receptor and leptin levels in pregnant women before and after delivery. Endocrine Res. 2004;30:379–85.

    CAS  Google Scholar 

  39. Misra VK, Trudeau S. The influence of overweight and obesity on longitudinal trends in maternal serum leptin levels during pregnancy. Obesity. 2011;19:416–21.

    CAS  PubMed  Google Scholar 

  40. Butte N, Hopkinson J, Nicolson M. Leptin in human reproduction: serum leptin levels in pregnant and lactating women. J Clin Endocrinol Metab. 1997;82:585–9.

    CAS  PubMed  Google Scholar 

  41. Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H, et al. Nonadipose tissue production of leptin: leptin as a novel placenta derived hormone in humans. Nat Med. 1997;3:1029–33.

    CAS  PubMed  Google Scholar 

  42. Sagawa N, Yura S, Itoh H, Kakui K, Takemura M, Nuamah MA, et al. Possible role of placental leptin in pregnancy. Endocrine. 2002;19:65–71.

    CAS  PubMed  Google Scholar 

  43. Fuglsang J, Skjærbæk C, Frystyk J, Flyvbjerg A, Ovesen P. A longitudinal study of serum adiponectin during normal pregnancy. BJOG. 2006;113:110–3.

    CAS  PubMed  Google Scholar 

  44. Henriksson P, Lof M, Forsum E. Parental fat-free mass is related to the fat-free mass of infants and maternal fat mass is related to the fat mass of infant girls. Acta Paediatr. 2015;104:491–7.

    PubMed  Google Scholar 

  45. Rode L, Kjærgaard H, Ottesen B, Damm P, Hegaard HK. Association between gestational weight gain according to body mass index and postpartum weight in a large cohort of Danish women. Mat Child Health J. 2012;16:406–13.

    Google Scholar 

  46. Löf M, Hilakivi-Clarke L, Sandin S, Weiderpass E. Effects of pre-pregnancy physical activity and maternal BMI on gestational weight gain and birth weight. Acta Obst et Gynecol Scand. 2008;87:524–30.

    Google Scholar 

  47. Moll U, Olsson H, Landin-Olsson M. Impact of pregestational weight and weight gain during pregnancy on long-term risk for diseases. PLoS ONE. 2017;12:e0168543.

    PubMed  PubMed Central  Google Scholar 

  48. Ronnberg A, Hanson U, Ostlund I, Nilsson K. Effects on postpartum weight retention after antenatal lifestyle intervention–a secondary analysis of a randomized controlled trial. Acta Obst et Gynecol Scand. 2016;95:999–1007.

    Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Emil and Wera Cornell Foundation, the Swedish Research Council (12206), the Swedish Diabetes Association Research Foundation (2015-08) and the Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement (720851). We would also like to thank all participating women of the PONCH study, and registered dietician Evelina Järvinen for expert caretaking and measurements during study visits.

Author information

Authors and Affiliations

  1. Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, 405 30, Gothenburg, Sweden

    Ulrika Andersson-Hall, Pernilla Svedin, Carina Mallard & Agneta Holmäng

  2. Institute of Biomedicine, Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30, Gothenburg, Sweden

    Henrik Svensson & Malin Lönn

  3. Department of Clinical Chemistry, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden

    Malin Lönn

Authors
  1. Ulrika Andersson-Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pernilla Svedin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Henrik Svensson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Malin Lönn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carina Mallard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Agneta Holmäng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ulrika Andersson-Hall.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Andersson-Hall, U., Svedin, P., Svensson, H. et al. Longitudinal changes in adipokines and free leptin index during and after pregnancy in women with obesity. Int J Obes 44, 675–683 (2020). https://doi.org/10.1038/s41366-019-0452-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-019-0452-7

This article is cited by

Search

Advanced search

Quick links