Abstract
Background:
Gestational diabetes mellitus (GDM) has long-lasting influence on offspring, which is associated with increased risks of insulin resistance, obesity, and type II diabetes mellitus. Calorie restriction (CR) is one of the most common and available nutritional interventions to prevent obesity and diabetes. We are trying to explore the effect of CR on GDM offspring.
Methods:
The streptozotocin was used to stimulate C57BL/6J mice to develop GDM, a number of metabolic characteristics and related protein expressions were determined in GDM offspring that were fed ad-libitum or treated with calorie restriction.
Results:
CR reduced body weight and glucose levels in GDM offspring. CR modulated the lipid metabolism by decreasing triglyceride and cholesterol levels in plasma. We also found that the effect of CR on insulin sensitivity may involve in signaling pathway through the regulations of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and protein kinase B (Akt).
Conclusion:
GDM is a high risk factor for GDM offspring to develop insulin resistance, while CR could ameliorate this adverse outcome. Moreover, the specific decrease in PTEN activation and increase in Akt phosphorylation in livers of GDM offspring with CR improved insulin sensitivity and lipid metabolism.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Reece EA, Leguizamón G, Wiznitzer A. Gestational diabetes: the need for a common ground. Lancet 2009;373:1789–97.
Ajala O, Jensen LA, Ryan E, Chik C. Women with a history of gestational diabetes on long-term follow up have normal vascular function despite more dysglycemia, dyslipidemia, and adiposity. Diabetes Res Clin Pract 2015;110:309–14.
Sreelakshmi PR, Nair S, Soman B, Alex R, Vijayakumar K, Kutty VR. Maternal and neonatal outcomes of gestational diabetes: a retrospective cohort study from Southern India. J Family Med Prim Care 2015;4:395–8.
Pereira TJ, Moyce BL, Kereliuk SM, Dolinsky VW. Influence of maternal overnutrition and gestational diabetes on the programming of metabolic health outcomes in the offspring: experimental evidence. Biochem Cell Biol 2014:1–14.
Quilter CR, Cooper WN, Cliffe KM, et al. Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk. FASEB J 2014;28:4868–79.
Pettitt DJ, Nelson RG, Saad MF, Bennett PH, Knowler WC. Diabetes and obesity in the offspring of Pima Indian women with diabetes during pregnancy. Diabetes Care 1993;16:310–4.
Meehan CA, Cochran E, Mattingly M, Gorden P, Brown RJ. Mild caloric restriction decreases insulin requirements in patients with type 2 diabetes and severe insulin resistance. Medicine (Baltimore) 2015;94:e1160.
Lara-Castro C, Newcomer BR, Rowell J, et al. Effects of short-term very low-calorie diet on intramyocellular lipid and insulin sensitivity in nondiabetic and type 2 diabetic subjects. Metabolism 2008;57:1–8.
Speakman JR, Mitchell SE. Caloric restriction. Mol Aspects Med 2011;32:159–221.
Ravussin E, Redman LM, Rochon J, et al.; CALERIE Study Group. A 2-year randomized controlled trial of human caloric restriction: feasibility and effects on predictors of health span and longevity. J Gerontol A Biol Sci Med Sci 2015;70:1097–104.
Dolinsky VW, Dyck JR. Calorie restriction and resveratrol in cardiovascular health and disease. Biochim Biophys Acta 2011;1812:1477–89.
Wang P, Zhang RY, Song J, et al. Loss of AMP-activated protein kinase-α2 impairs the insulin-sensitizing effect of calorie restriction in skeletal muscle. Diabetes 2012;61:1051–61.
Bales CW, Kraus WE. Caloric restriction: implications for human cardiometabolic health. J Cardiopulm Rehabil Prev 2013;33:201–8.
Schenk S, McCurdy CE, Philp A, et al. Sirt1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction. J Clin Invest 2011;121:4281–8.
GarcÃa-San Frutos M, Fernández-Agulló T, Carrascosa JM, et al. Involvement of protein tyrosine phosphatases and inflammation in hypothalamic insulin resistance associated with ageing: effect of caloric restriction. Mech Ageing Dev 2012;133:489–97.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.
Molin M, Demir AB. Linking peroxiredoxin and vacuolar-ATPase functions in calorie restriction-mediated life span extension. Int J Cell Biol 2014;2014:913071.
Rona G, Herdeiro R, Mathias CJ, Torres FA, Pereira MD, Eleutherio E. CTT1 overexpression increases life span of calorie-restricted Saccharomyces cerevisiae deficient in Sod1. Biogerontology 2015;16:343–51.
Kroeger CM, Klempel MC, Bhutani S, Trepanowski JF, Tangney CC, Varady KA. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: relationship to adipokine modulations. Nutr Metab (Lond) 2012;9:98.
Weiss EP, Fontana L. Caloric restriction: powerful protection for the aging heart and vasculature. Am J Physiol Heart Circ Physiol 2011;301:H1205–19.
Kirk E, Reeds DN, Finck BN, et al. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology 2009;136:1552–60.
Lee CK, Allison DB, Brand J, Weindruch R, Prolla TA. Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts. Proc Natl Acad Sci USA 2002;99:14988–93.
Dabelea D. The predisposition to obesity and diabetes in offspring of diabetic mothers. Diabetes Care 2007;30 Suppl 2:S169–74.
Deng HZ, Deng H, Cen CQ, Chen KY, Du ML. Post-receptor crosstalk between growth hormone and insulin signal in rats born small for gestational age with catch-up growth. PLoS One 2014;9:e100459.
Alves JG, Vasconcelos SA, de Almeida TS, Lages R, Just E. Influence of catch-up growth on abdominal fat distribution in very low birth weight children—cohort study. J Pediatr Endocrinol Metab 2015;28:153–6.
Kuhla A, Hahn S, Butschkau A, Lange S, Wree A, Vollmar B. Lifelong caloric restriction reprograms hepatic fat metabolism in mice. J Gerontol A Biol Sci Med Sci 2014;69:915–22.
Wu X, Chen K, Williams KJ. The role of pathway-selective insulin resistance and responsiveness in diabetic dyslipoproteinemia. Curr Opin Lipidol 2012;23:334–44.
Han C, Wei S, He F, et al. The regulation of lipid deposition by insulin in goose liver cells is mediated by the PI3K-AKT-mTOR signaling pathway. PLoS One 2015;10:e0098759.
Staff PG. Correction: Maf1 is a novel target of PTEN and PI3K signaling that negatively regulates oncogenesis and lipid metabolism. PLOS Genetics Staff 2015;11:e1005055.
Davidson RT, Arias EB, Cartee GD. Calorie restriction increases muscle insulin action but not IRS-1-, IRS-2-, or phosphotyrosine-PI 3-kinase. Am J Physiol Endocrinol Metab 2002;282:E270–6.
McCurdy CE, Davidson RT, Cartee GD. Brief calorie restriction increases Akt2 phosphorylation in insulin-stimulated rat skeletal muscle. Am J Physiol Endocrinol Metab 2003;285:E693–700.
Reynolds THt, Merrell E, Cinquino N, Gaugler M, Ng L. Disassociation of insulin action and Akt/FOXO signaling in skeletal muscle of older Akt-deficient mice. Am J Physiol Regul Integr Comp Physiol 2012;303:R1186–94.
Cho H, Mu J, Kim JK, et al. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science 2001;292:1728–31.
Park H, Lee S, Shrestha P, et al. AMIGO2, a novel membrane anchor of PDK1, controls cell survival and angiogenesis via Akt activation. J Cell Biol 2015;211:619–37.
Pearn L, Fisher J, Burnett AK, Darley RL. The role of PKC and PDK1 in monocyte lineage specification by Ras. Blood 2007;109:4461–9.
Yang J, Cron P, Thompson V, et al. Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation. Mol Cell 2002;9:1227–40.
Maehama T, Dixon JE. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 1998;273:13375–8.
Shibata E, Kanno T, Tsuchiya A, et al. Free fatty acids inhibit protein tyrosine phosphatase 1B and activate Akt. Cell Physiol Biochem 2013;32:871–9.
Wang Q, Li S, Jiang L, et al. Deficiency in hepatic ATP-citrate lyase affects VLDL-triglyceride mobilization and liver fatty acid composition in mice. J Lipid Res 2010;51:2516–26.
Lemus HN, Mendivil CO. Adenosine triphosphate citrate lyase: emerging target in the treatment of dyslipidemia. J Clin Lipidol 2015;9:384–9.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Li, T., Chen, K., Liu, G. et al. Calorie restriction prevents the development of insulin resistance and impaired lipid metabolism in gestational diabetes offspring. Pediatr Res 81, 663–671 (2017). https://doi.org/10.1038/pr.2016.273
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2016.273
This article is cited by
-
Caloric restriction leads to druggable LSD1-dependent cancer stem cells expansion
Nature Communications (2024)
-
Protective effects of calorie restriction on insulin resistance and islet function in STZ-induced type 2 diabetes rats
Nutrition & Metabolism (2021)
-
The Placental Transcriptome in Late Gestational Hypoxia Resulting in Murine Intrauterine Growth Restriction Parallels Increased Risk of Adult Cardiometabolic Disease
Scientific Reports (2019)