Normalizing Adiponectin Levels in Obese Pregnant Mice Prevents Adverse Metabolic Outcomes in Offspring

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2018 Oct 23

PMID 30346829

Citations 24

Authors

Megan E Paulsen

Fredrick J Rosario

Stephanie R Wesolowski

Theresa L Powell

Thomas Jansson

Affiliations

Soon will be listed here.

Abstract

Infants of obese mothers have an increased risk of developing obesity, insulin resistance, and type 2 diabetes. The underlying mechanisms remain elusive, and no effective interventions to limit the transmission of metabolic disease from the obese mother to her infant are currently available. Obese pregnant women have decreased circulating levels of adiponectin, which is associated with increased placental nutrient transport and fetal overgrowth. We have reported that normalization of adiponectin levels during late gestation reversed placental dysfunction and fetal overgrowth in a mouse model of maternal obesity in pregnancy. In the current study, we hypothesized that adiponectin supplementation during pregnancy in obese mice attenuates the adverse metabolic outcomes in adult offspring. Adult male offspring of obese mice developed obesity, fatty liver, and insulin resistance, with adult female offspring of obese mice having a less pronounced metabolic phenotype. These metabolic abnormalities in offspring born to obese mice were largely prevented by normalization of maternal adiponectin levels in late pregnancy. We provide evidence that low circulating maternal adiponectin is a critical mechanistic link between maternal obesity and the development of metabolic disease in offspring. Strategies aimed at improving maternal adiponectin levels may prevent long-term metabolic dysfunction in offspring of obese mothers.-Paulsen, M. E., Rosario, F. J., Wesolowski, S. R., Powell, T. L., Jansson, T. Normalizing adiponectin levels in obese pregnant mice prevents adverse metabolic outcomes in offspring.

Citing Articles

THRA1/PGC-1α/SIRT3 pathway regulates oxidative stress and is implicated in hypertension of maternal hypothyroid rat offspring.

Guo J, Shi Y, Yu X, Zhao Y, Wei B, Huo M Hypertens Res. 2024; 48(3):1080-1098.

PMID: 39639130 DOI: 10.1038/s41440-024-02023-9.

Trophoblast-specific overexpression of adiponectin receptor 2 causes fetal growth restriction in pregnant mice.

Dumolt J, Rosario F, Barentsen K, Urschitz J, Powell T, Jansson T FASEB J. 2024; 38(19):e70100.

PMID: 39387608 PMC: 11508969. DOI: 10.1096/fj.202302143R.

Initiation of metformin in early pregnancy results in fetal bioaccumulation, growth restriction, and renal dysmorphology in a primate model.

Bolte E, Dean T, Garcia B, Seferovic M, Sauter K, Hummel G Am J Obstet Gynecol. 2024; 231(3):352.e1-352.e16.

PMID: 38871238 PMC: 11344684. DOI: 10.1016/j.ajog.2024.06.002.

Long-term impact of maternal obesity on the gliovascular unit and ephrin signaling in the hippocampus of adult offspring.

Jabbari Shiadeh S, Goretta F, Svedin P, Jansson T, Mallard C, Ardalan M J Neuroinflammation. 2024; 21(1):39.

PMID: 38308309 PMC: 10837922. DOI: 10.1186/s12974-024-03030-w.

Kinin B1 receptor controls maternal adiponectin levels and influences offspring weight gain.

Alves-Silva T, Hungaro T, Freitas-Lima L, de Melo Arthur G, Arruda A, Santos R iScience. 2023; 26(12):108409.

PMID: 38058311 PMC: 10696114. DOI: 10.1016/j.isci.2023.108409.

References

Stoffers D, Desai B, DeLeon D, Simmons R . Neonatal exendin-4 prevents the development of diabetes in the intrauterine growth retarded rat. Diabetes. 2003; 52(3):734-40. DOI: 10.2337/diabetes.52.3.734. View

Leto D, Saltiel A . Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol Cell Biol. 2012; 13(6):383-96. DOI: 10.1038/nrm3351. View

Ategbo J, Grissa O, Yessoufou A, Hichami A, Dramane K, Moutairou K . Modulation of adipokines and cytokines in gestational diabetes and macrosomia. J Clin Endocrinol Metab. 2006; 91(10):4137-43. DOI: 10.1210/jc.2006-0980. View

Thornburg K, Kolahi K, Pierce M, Valent A, Drake R, Louey S . Biological features of placental programming. Placenta. 2016; 48 Suppl 1:S47-S53. PMC: 5278807. DOI: 10.1016/j.placenta.2016.10.012. View

Gabory A, Ferry L, Fajardy I, Jouneau L, Gothie J, Vige A . Maternal diets trigger sex-specific divergent trajectories of gene expression and epigenetic systems in mouse placenta. PLoS One. 2012; 7(11):e47986. PMC: 3489896. DOI: 10.1371/journal.pone.0047986. View

Retnakaran R, Qi Y, Connelly P, Sermer M, Hanley A, Zinman B . Low adiponectin concentration during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia. Diabetologia. 2009; 53(2):268-76. PMC: 2878328. DOI: 10.1007/s00125-009-1600-8. View

Vatner D, Majumdar S, Kumashiro N, Petersen M, Rahimi Y, Gattu A . Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids. Proc Natl Acad Sci U S A. 2015; 112(4):1143-8. PMC: 4313795. DOI: 10.1073/pnas.1423952112. View

Gluckman P, Hanson M . Living with the past: evolution, development, and patterns of disease. Science. 2004; 305(5691):1733-6. DOI: 10.1126/science.1095292. View

Wang X, Liang L, Junfen F, Lizhong D . Metabolic syndrome in obese children born large for gestational age. Indian J Pediatr. 2007; 74(6):561-5. DOI: 10.1007/s12098-007-0108-9. View

10.

Tsai P, Yu C, Hsu S, Lee Y, Huang I, Ho S . Maternal plasma adiponectin concentrations at 24 to 31 weeks of gestation: negative association with gestational diabetes mellitus. Nutrition. 2005; 21(11-12):1095-9. DOI: 10.1016/j.nut.2005.03.008. View

11.

Bomba-Opon D, Wielgos M, Horosz E, Bartkowiak R, Szymusik I, Mazanowski N . Maternal plasma cytokines concentrations and insulin resistance in first trimester in relation to fetal growth. Neuro Endocrinol Lett. 2009; 30(6):729-32. View

12.

Qiao L, Wattez J, Lee S, Guo Z, Schaack J, Hay Jr W . Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1. Diabetologia. 2016; 59(11):2417-2425. PMC: 5042853. DOI: 10.1007/s00125-016-4061-x. View

13.

Ahlsson F, Diderholm B, Ewald U, Gustafsson J . Lipolysis and insulin sensitivity at birth in infants who are large for gestational age. Pediatrics. 2007; 120(5):958-65. DOI: 10.1542/peds.2007-0165. View

14.

Qiao L, Wattez J, Lee S, Nguyen A, Schaack J, Hay Jr W . Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice. Diabetes. 2017; 66(5):1126-1135. PMC: 5399613. DOI: 10.2337/db16-1096. View

15.

Aye I, Rosario F, Powell T, Jansson T . Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth. Proc Natl Acad Sci U S A. 2015; 112(41):12858-63. PMC: 4611638. DOI: 10.1073/pnas.1515484112. View

16.

Stocker C, Wargent E, ODowd J, Cornick C, Speakman J, Arch J . Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers. Am J Physiol Regul Integr Comp Physiol. 2007; 292(5):R1810-8. DOI: 10.1152/ajpregu.00676.2006. View

17.

Berg A, Combs T, Scherer P . ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab. 2002; 13(2):84-9. DOI: 10.1016/s1043-2760(01)00524-0. View

18.

Stocker C, ODowd J, Morton N, Wargent E, Sennitt M, Hislop D . Modulation of susceptibility to weight gain and insulin resistance in low birthweight rats by treatment of their mothers with leptin during pregnancy and lactation. Int J Obes Relat Metab Disord. 2003; 28(1):129-36. DOI: 10.1038/sj.ijo.0802476. View

19.

Thorn S, Baquero K, Newsom S, El Kasmi K, Bergman B, Shulman G . Early life exposure to maternal insulin resistance has persistent effects on hepatic NAFLD in juvenile nonhuman primates. Diabetes. 2014; 63(8):2702-13. PMC: 4113070. DOI: 10.2337/db14-0276. View

20.

Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K . A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature. 2013; 503(7477):493-9. DOI: 10.1038/nature12656. View