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CC BY-NC-ND 4.0 · Am J Perinatol 2023; 40(04): 400-406
DOI: 10.1055/s-0041-1728828
Original Article

SERUM GLP-2 is Increased in Association with Excess Gestational Weight Gain

Maike K. Kahr
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas
2   Department of Obstetrics and Gynecology, University Hospital Zurich, Zurich, Switzerland
,
Kathleen M. Antony 
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas
3   Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, Wisconsin
,
Megan Galindo
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas
,
Megan Whitham
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas
,
Min Hu
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas
,
Kjersti M. Aagaard
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas
,
Melissa A. Suter
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas
› Author Affiliations Funding This work was funded by a pilot award from the Texas Medical Center Digestive Disease Center (P30DK56338 to M.A.S.), a grant from the U.S. Department of Health and Human Services, National Institutes of Health NIH/NICHD (R00HD075858–03 to M.A.S), and the German Research Foundation (Deutsche Forschungsgemeinschaft DFG, SA 2795/2–1 to M.K.K.).
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Abstract

Objective Obesity in pregnancy bears unique maternal and fetal risks. Obesity has also been associated with chronic inflammation, including elevated serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher serum lipopolysaccharide (LPS) levels have been implicated in driving this inflammation, a phenomenon called metabolic endotoxemia (ME). GLP-2, a proglucagon-derived peptide, is believed to be integral in maintaining the integrity of the intestine in the face of LPS-mediated endotoxemia. We hypothesized that obesity and/or excess weight gain in pregnancy would be associated with an increase in maternal and neonatal markers of ME, as well as GLP-2.

Study Design Paired maternal and neonatal (cord blood) serum samples (n = 159) were obtained from our pregnancy biobank repository. Serum levels of LPS, endotoxin core antibody-immunoglobulin M (EndoCAb-IgM), and GLP-2 were measured by ELISA. IL-6 and TNF-α were measured using a Milliplex assay. Results were stratified by maternal body mass index (BMI), maternal diabetes, and gestational weight gain (GWG).

Results Maternal IL-6 is significantly decreased in the obese, diabetic cohort compared with the nonobese, nondiabetic cohorts (95.28 vs. 99.48 pg/mL, p = 0.047), whereas GLP-2 is significantly increased (1.92 vs. 2.89 ng/mL, p = 0.026). Neonatal TNF-α is significantly decreased in the obese cohort compared with the nonobese cohort (12.43 vs. 13.93 pg/mL, p = 0.044). Maternal GLP-2 is significantly increased in women with excess GWG compared with those with normal GWG (2.27 vs. 1.48 ng/mL, p = 0.014). We further found that neonatal IL-6 and TNF-α are negatively correlated with maternal BMI (–0.186, p = 0.036 and –0.179, p = 0.044, respectively) and that maternal and neonatal IL-6 showed a positive correlation (0.348, p < 0.001).

Conclusion Although we observed altered levels of markers of inflammation (IL-6 and TNF-α) with maternal obesity and diabetes, no changes in LPS or endoCAb-IgM were observed. We hypothesize that the increased GLP-2 levels in maternal serum in association with excess GWG may protect against ME in pregnancy.

Key Points

  • Maternal serum levels of GLP-2, a proglucagon-derived peptide, are increased in obese, diabetic gravidae.

  • Maternal serum GLP-2 levels are also increased in association with excess gestational weight gain compared with normal gestational weight gain.

  • GLP-2 may be increased in association with obesity and weight gain to protect against metabolic endotoxemia in pregnancy.

Keywords

gestational weight gain - gestational diabetes - obesity - metabolic endotoxemia

Supplementary Material



Publication History

Received: 10 June 2020

Accepted: 02 March 2021

Article published online:
03 May 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Kassi E, Pervanidou P, Kaltsas G, Chrousos G. Metabolic syndrome: definitions and controversies. BMC Med 2011; 9: 48
    CrossrefPubMedGoogle Scholar
  • 2 Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006; 116 (07) 1793-1801
    CrossrefPubMedGoogle Scholar
  • 3 Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001; 280 (05) E745-E751
    CrossrefPubMedGoogle Scholar
  • 4 Cani PD, Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des 2009; 15 (13) 1546-1558
    CrossrefPubMedGoogle Scholar
  • 5 Cani PD, Amar J, Iglesias MA. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007; 56 (07) 1761-1772
    CrossrefPubMedGoogle Scholar
  • 6 Laugerette F, Vors C, Peretti N, Michalski MC. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation. Biochimie 2011; 93 (01) 39-45
    CrossrefPubMedGoogle Scholar
  • 7 Neves AL, Coelho J, Couto L, Leite-Moreira A, Roncon-Albuquerque Jr R. Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk. J Mol Endocrinol 2013; 51 (02) R51-R64
    CrossrefPubMedGoogle Scholar
  • 8 Hawkesworth S, Moore SE, Fulford AJ. et al. Evidence for metabolic endotoxemia in obese and diabetic Gambian women. Nutr Diabetes 2013; 3: e83
    CrossrefPubMedGoogle Scholar
  • 9 Benjamin MA, McKay DM, Yang PC, Cameron H, Perdue MH. Glucagon-like peptide-2 enhances intestinal epithelial barrier function of both transcellular and paracellular pathways in the mouse. Gut 2000; 47 (01) 112-119
    CrossrefPubMedGoogle Scholar
  • 10 Cani PD, Possemiers S, Van de Wiele T. et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009; 58 (08) 1091-1103
    CrossrefPubMedGoogle Scholar
  • 11 Maruta K, Takajo T, Akiba Y. et al. GLP-2 acutely prevents endotoxin-related increased intestinal paracellular permeability in rats. Dig Dis Sci 2020; 65 (09) 2605-2618
    CrossrefPubMedGoogle Scholar
  • 12 Moyce BL, Dolinsky VW. Maternal β-cell adaptations in pregnancy and placental signalling: implications for gestational diabetes. Int J Mol Sci 2018; 19 (11) E3467
    CrossrefPubMedGoogle Scholar
  • 13 Ernst S, Demirci C, Valle S, Velazquez-Garcia S, Garcia-Ocaña A. Mechanisms in the adaptation of maternal β-cells during pregnancy. Diabetes Manag (Lond) 2011; 1 (02) 239-248
    CrossrefPubMedGoogle Scholar
  • 14 Yogev Y, Catalano PM. Pregnancy and obesity. Obstet Gynecol Clin North Am 2009; 36 (02) 285-300 , viii
    CrossrefPubMedGoogle Scholar
  • 15 Aviram A, Hod M, Yogev Y. Maternal obesity: implications for pregnancy outcome and long-term risks-a link to maternal nutrition. Int J Gynaecol Obstet 2011; 115 (Suppl. 01) S6-S10
    CrossrefPubMedGoogle Scholar
  • 16 Zhu Y, Zhang C. Prevalence of gestational diabetes and risk of progression to type 2 diabetes: a global perspective. Curr Diab Rep 2016; 16 (01) 7
    CrossrefPubMedGoogle Scholar
  • 17 Johnson J, Clifton RG, Roberts JM. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network*. Pregnancy outcomes with weight gain above or below the 2009 Institute of Medicine guidelines. Obstet Gynecol 2013; 121 (05) 969-975
    CrossrefPubMedGoogle Scholar
  • 18 Basu S, Haghiac M, Surace P. et al. Pregravid obesity associates with increased maternal endotoxemia and metabolic inflammation. Obesity (Silver Spring) 2011; 19 (03) 476-482
    CrossrefPubMedGoogle Scholar
  • 19 Hanson M, Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD. Developmental plasticity and developmental origins of non-communicable disease: theoretical considerations and epigenetic mechanisms. Prog Biophys Mol Biol 2011; 106 (01) 272-280
    CrossrefPubMedGoogle Scholar
  • 20 Suter MA, Aagaard-Tillery KM. Environmental influences on epigenetic profiles. Semin Reprod Med 2009; 27 (05) 380-390
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Antony KM, Hemarajata P, Chen J. et al. Generation and validation of a universal perinatal database and biospecimen repository: PeriBank. J Perinatol 2016; 36 (11) 921-929
    CrossrefPubMedGoogle Scholar
  • 22 Chabarria KC, Racusin DA, Antony KM. et al. Marijuana use and its effects in pregnancy. Am J Obstet Gynecol 2016; 215 (04) 506
    CrossrefPubMedGoogle Scholar
  • 23 Kahr MK, Suter MA, Ballas J. et al. Preterm birth and its associations with residence and ambient vehicular traffic exposure. Am J Obstet Gynecol 2016; 215 (01) 111
    PubMedGoogle Scholar
  • 24 Kahr MK, Suter MA, Ballas J. et al. Geospatial analysis of food environment demonstrates associations with gestational diabetes. Am J Obstet Gynecol 2016; 214 (01) 110
    PubMedGoogle Scholar
  • 25 Kahr MK, Antony KM, DelBeccaro M, Hu M, Aagaard KM, Suter MA. Increasing maternal obesity is associated with alterations in both maternal and neonatal thyroid hormone levels. Clin Endocrinol (Oxf) 2016; 84 (04) 551-557
    CrossrefPubMedGoogle Scholar
  • 26 American College of Obstetricians and Gynecologists. ACOG Committee opinion no. 548: weight gain during pregnancy. Obstet Gynecol 2013; 121 (01) 210-212
    CrossrefPubMedGoogle Scholar
  • 27 Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982; 144 (07) 768-773
    CrossrefPubMedGoogle Scholar
  • 28 Mack LR, Tomich PG. Gestational diabetes: diagnosis, classification, and clinical care. Obstet Gynecol Clin North Am 2017; 44 (02) 207-217
    CrossrefPubMedGoogle Scholar
  • 29 Powers R, Kotchey N, Gandley R, Jeyabalan A, Hubel C. PP180. Maternal plasma endotoxin increases significantly across pregnancy with no association with obesity, inflammation, or insulin sensitivity. Pregnancy Hypertens 2012; 2 (03) 337-338
    CrossrefPubMedGoogle Scholar
  • 30 Mokkala K, Pellonperä O, Röytiö H, Pussinen P, Rönnemaa T, Laitinen K. Increased intestinal permeability, measured by serum zonulin, is associated with metabolic risk markers in overweight pregnant women. Metabolism 2017; 69: 43-50
    CrossrefPubMedGoogle Scholar
  • 31 Zaretsky MV, Alexander JM, Byrd W, Bawdon RE. Transfer of inflammatory cytokines across the placenta. Obstet Gynecol 2004; 103 (03) 546-550
    CrossrefPubMedGoogle Scholar
  • 32 Ben-Hur H, Gurevich P, Elhayany A, Avinoach I, Schneider DF, Zusman I. Transport of maternal immunoglobulins through the human placental barrier in normal pregnancy and during inflammation. Int J Mol Med 2005; 16 (03) 401-407
    PubMedGoogle Scholar
  • 33 Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med 2014; 6 (237) 237ra65
    CrossrefPubMedGoogle Scholar
  • 34 Prince AL, Chu DM, Seferovic MD, Antony KM, Ma J, Aagaard KM. The perinatal microbiome and pregnancy: moving beyond the vaginal microbiome. Cold Spring Harb Perspect Med 2015; 5 (06) a023051
    CrossrefPubMedGoogle Scholar
  • 35 Antony KM, Ma J, Mitchell KB, Racusin DA, Versalovic J, Aagaard K. The preterm placental microbiome varies in association with excess maternal gestational weight gain. Am J Obstet Gynecol 2015; 212 (05) 653
    CrossrefPubMedGoogle Scholar