Influences of maternal obesity on the health of the offspring: a review of animal models

doi:10.1017/CBO9780511782466.011

10 - Influences of maternal obesity on the health of the offspring: a review of animal models

from Section 3 - Long-term consequences

Published online by Cambridge University Press: 05 August 2012

Lucilla Poston ,

Paul D. Taylor and

Peter Nathanielsz

Edited by

Matthew W. Gillman and

Lucilla Poston

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Matthew W. Gillman: Affiliation:
Harvard Medical School
Lucilla Poston: Affiliation:
King's College London

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Summary

Introduction

The prevalence of obesity among women worldwide (Figure 1.1; Chapter 1) is a cause for serious concern, not only for the mother’s health but also that of her children, whether a result of the immediate risk of complications in pregnancy or from more subtle influences on the developing child (Chapters 9, 11, 12, and 13). In this chapter we provide a summary of the role that animal models have played in contributing to our understanding of potential influences of maternal obesity on offspring health in later life.

As described in Chapter 9, many observational studies in mother/child cohorts have reported an independent association between maternal BMI and offspring BMI in childhood and adulthood [1,2], but the expected predominance of maternal obesity vs. paternal obesity in parent–child obesity relationships is not always apparent [3,4]. Alternative explanations for mother–child associations of obesity are that the child inherits obesogenic genes or that they share similar postnatal environments. There is also some suggestion that maternal obesity is associated with the risk of elevated blood pressure and cardiovascular disease in childhood and beyond, but this is limited to a few reports [5–8]. Intervention studies in obese women before or during pregnancy, with follow-up of the children, are likely to provide the strongest test of the hypothesis that obesity per se causes adverse offspring outcomes. Observational studies of siblings whose mothers achieved weight loss through bariatric surgery certainly provide some support; the sibling born to the mother before surgery is more at risk of obesity than the brother or sister born after maternal weight loss [9]. However, randomized controlled trials of interventions have yet to report and in the meantime the theory that obesity in the pregnant woman directly increases the risk of obesity and related disorders through influences on the unborn child remains to be proven.

Keywords

animal models cardiovascular function maternal obesity placental transfer metabolites offspring

Type: Chapter
Information: Maternal Obesity , pp. 100 - 114

DOI: https://doi.org/10.1017/CBO9780511782466.011 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2012

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References

Salsberry, P J Reagan, P B Dynamics of early childhood overweight Pediatrics 2005 116 1329 Google Scholar

Whitaker, R C Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy Pediatrics 2004 114(1) e29 Google Scholar

Lawlor, D A Timpson, N J Harbord, R M Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable PLoS Med 2008 5(3) e33 Google Scholar

Patel, R Martin, R M Kramer, M S Familial associations of adiposity: findings from a cross-sectional study of 12,181 parental-offspring trios from Belarus PLoS One 2011 6(1) e14607 Google Scholar

Forsen, T Eriksson, J G Tuomilehto, J Mother’s weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study BMJ 1997 315 837 Google Scholar

Boney, C M Verma, A Tucker, R Vohr, B R Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus Pediatrics 2005 115 e290 Google Scholar

Lawlor, D A Najman, J M Sterne, J Associations of parental, birth, and early life characteristics with systolic blood pressure at 5 years of age: findings from the Mater-University study of pregnancy and its outcomes Circulation 2004 110 2417 Google Scholar

Mamun, A A O’Callaghan, M Callaway, L Associations of gestational weight gain with offspring body mass index and blood pressure at 21 years of age: evidence from a birth cohort study Circulation 2009 119 1720 Google Scholar

Smith, J Cianflone, K Biron, S Effects of maternal surgical weight loss in mothers on intergenerational transmission of obesity J Clin Endocrinol Metab 2009 94 4275 Google Scholar

Armitage, J A Khan, I Y Taylor, P D Nathanielsz, P W Poston, L Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol 2004 561 355 Google Scholar

Remmers, F Delemarre-van de Waal, H A Developmental programming of energy balance and its hypothalamic regulation Endocr Rev 2011 32 272 Google Scholar

Sullivan, E L Smith, M S Grove, K L Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood Neuroendocrinology 2011 93 1 Google Scholar

Bayol, S A Simbi, B H Stickland, N C A maternal cafeteria diet during gestation and lactation promotes adiposity and impairs skeletal muscle development and metabolism in rat offspring at weaning J Physiol 2005 567 951 Google Scholar

Akyol, A Langley-Evans, S C McMullen, S Obesity induced by cafeteria feeding and pregnancy outcome in the rat Br J Nutr 2009 102 1601 Google Scholar

Samuelsson, A M Matthews, P A Argenton, M Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming Hypertension 2008 51 383 Google Scholar

Taylor, P D Khan, I Y Lakasing, L Uterine artery function in pregnant rats fed a diet supplemented with animal lard Exp Physiol 2003 88 389 Google Scholar

Srinivasan, M Katewa, S D Palaniyappan, A Pandya, J D Patel, M S Maternal high-fat diet consumption results in fetal malprogramming predisposing to the onset of metabolic syndrome-like phenotype in adulthood Am J Physiol Endocrinol Metab 2006 291 e792 Google Scholar

Nivoit, P Morens, C Van Assche, F A Established diet-induced obesity in female rats leads to offspring hyperphagia, adiposity and insulin resistance Diabetologia 2009 52 1133 Google Scholar

Holemans, K Caluwaerts, S Poston, L Van Assche, F A Diet-induced obesity in the rat: a model for gestational diabetes mellitus Am J Obstet Gynecol 2004 190 858 Google Scholar

Chen, H Simar, D Lambert, K Mercier, J Morris, M J Maternal and postnatal overnutrition differentially impact appetite regulators and fuel metabolism Endocrinology 2008 149 5348 Google Scholar

Muhlhausler, B S Duffield, J A McMillen, I C Increased maternal nutrition increases leptin expression in perirenal and subcutaneous adipose tissue in the postnatal lamb Endocrinology 2007 148 6157 Google Scholar

Long, N M George, L A Uthlaut, A B Maternal obesity and increased nutrient intake before and during gestation in the ewe results in altered growth, adiposity, and glucose tolerance in adult offspring J Anim Sci 2010 88 3546 Google Scholar

Rattanatray, L MacLaughlin, S M Kleemann, D O Impact of maternal periconceptional overnutrition on fat mass and expression of adipogenic and lipogenic genes in visceral and subcutaneous fat depots in the postnatal lamb Endocrinology 2010 151 5195 Google Scholar

McCurdy, C E Bishop, J M Williams, S M Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates J Clin Invest 2009 119 323 Google Scholar

Li, C Xie, L Choi, J Fetal baboon pituitary leptin and leptin receptor (Ob-R) are both down regulated by maternal nutrient excess (MN) Reproductive Sciences 2011 18 165A Google Scholar

Rajasingam, D Seed, P T Briley, A L Shennan, A H Poston, L A prospective study of pregnancy outcome and biomarkers of oxidative stress in nulliparous obese women Am J Obstet Gynecol 2009 200 395e1 Google Scholar

McDonald, S D Han, Z Mulla, S Beyene, J Overweight and obesity in mothers and risk of preterm birth and low birth weight infants: systematic review and meta-analyses BMJ 2010 341 c3428 Google Scholar

Ma, Y Zhu, M J Uthlaut, A B Upregulation of growth signaling and nutrient transporters in cotyledons of early to mid-gestational nutrient restricted ewes Placenta 2010 31 387 Google Scholar

Zhu, M J Du, M Nathanielsz, P W Ford, S P Maternal obesity up-regulates inflammatory signaling pathways and enhances cytokine expression in the mid-gestation sheep placenta Placenta 2011 32 255 Google Scholar

Frias, A E Morgan, T K Evans, A E Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition Endocrinology 2011 152 Google Scholar

Farley, D Tejero, M E Comuzzie, A G Feto-placental adaptations to maternal obesity in the baboon Placenta 2009 30 752 Google Scholar

Jones, H N Woollett, L A Barbour, N High-fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57/BL6 mice FASEB J 2009 23 271 Google Scholar

Nathanielsz, P W Wu, G Ford, S P Dysregulation of one carbon cycle (1CC) metabolites by maternal nutrient excess (MNE) in baboon pregnancy Reprod Sci 2011 18 334A Google Scholar

Akyol, A McMullen, S Langley-Evans, S C Glucose intolerance associated with early-life exposure to maternal cafeteria feeding is dependent upon post-weaning diet Br J Nutr 2011 1 Google Scholar

Bayol, S A Farrington, S J Stickland, N C A maternal ‘junk food’ diet in pregnancy and lactation promotes an exacerbated taste for ‘junk food’ and a greater propensity for obesity in rat offspring Br J Nutr 2007 98 843 Google Scholar

Chang, G Q Gaysinskaya, V Karatayev, O Leibowitz, S F Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity J Neurosci 2008 28 12107 Google Scholar

Dunn, G A Bale, T L Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice Endocrinology 2009 150 4999 Google Scholar

Ferezou-Viala, J Roy, A F Serougne, C Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensitivity and diet-induced obesity in the offspring Am J Physiol Regul Integr Comp Physiol 2007 293 R1056 Google Scholar

Levin, B E Govek, E Gestational obesity accentuates obesity in obesity-prone progeny Am J Physiol 1998 275 R1374 Google Scholar

Shankar, K Harrell, A Liu, X Maternal obesity at conception programs obesity in the offspring Am J Physiol Regul Integr Comp Physiol 2008 294 R528 Google Scholar

White, C L Purpera, M N Morrison, C D Maternal obesity is necessary for programming effect of high-fat diet on offspring Am J Physiol Regul Integr Comp Physiol 2009 296 R1464 Google Scholar

Carmody, J S Wan, P Accili, D Zeltser, L M Leibel, R L Respective contributions of maternal insulin resistance and diet to metabolic and hypothalamic phenotypes of progeny Obesity (Silver Spring) 2011 19 492 Google Scholar

Dong, Y M Li, Y Ning, H High dietary intake of medium-chain fatty acids during pregnancy in rats prevents later-life obesity in their offspring J Nutr Biochem 2010 22 791 Google Scholar

Korotkova, M Ohlsson, C Gabrielsson B, Hanson L A Strandvik, B Perinatal essential fatty acid deficiency influences body weight and bone parameters in adult male rats Biochim Biophys Acta 2005 1686 248 Google Scholar

Cryer, A Jones, H M The development of white adipose tissue. Effect of litter size on the lipoprotein lipase activity of four adipose-tissue depots, serum immunoreactive insulin and tissue cellularity during the first year of life in male and female rats Biochem J 1980 186 805 Google Scholar

Patel, M S Srinivasan, M Laychock, S G Metabolic programming: role of nutrition in the immediate postnatal life J Inherit Metab Dis 2009 32 218 Google Scholar

Ford, S P Zhang, L Zhu, M Maternal obesity accelerates fetal pancreatic beta-cell but not alpha-cell development in sheep: prenatal consequences Am J Physiol Regul Integr Comp Physiol 2009 297 R835 Google Scholar

Oben, J A Mouralidarane, A Samuelsson, A M Maternal obesity during pregnancy and lactation programs the development of offspring non-alcoholic fatty liver disease in mice J Hepatol 2010 52 913 Google Scholar

Del Prado, M Delgado, G Villalpando, S Maternal lipid intake during pregnancy and lactation alters milk composition and production and litter growth in rats J Nutr 1997 127 458 Google Scholar

Kirk, S L Samuelsson, A M Argenton, M Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring PLoS One 2009 4 e5870 Google Scholar

Chen, H Morris, M J Differential responses of orexigenic neuropeptides to fasting in offspring of obese mothers Obesity (Silver Spring) 2009 17 1356 Google Scholar

Chen, H Simar, D Morris, M J Hypothalamic neuroendocrine circuitry is programmed by maternal obesity: interaction with postnatal nutritional environment PLoS One 2009 4 e6259 Google Scholar

Plagemann, A Harder, T Hormonal programming in perinatal life: leptin and beyond Br J Nutr 2008 1 Google Scholar

Ong, Z Y Muhlhausler, B S Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring FASEB J 2011 25 2167 Google Scholar

Vucetic, Z Kimmel, J Totoki, K Hollenbeck, E Reyes, T M Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes Endocrinology 2010 151 4756 Google Scholar

Brion, M J Ness, A R Rogers, I Maternal macronutrient and energy intakes in pregnancy and offspring intake at 10 y: exploring parental comparisons and prenatal effects Am J Clin Nutr 2010 91 748 Google Scholar

Elmquist, J K Elias, C F Saper, C B From lesions to leptin: hypothalamic control of food intake and body weight Neuron 1999 22 221 Google Scholar

Spiegelman, B M Flier, J S Obesity and the regulation of energy balance Cell 2001 104 531 Google Scholar

Cone, R D Anatomy and regulation of the central melanocortin system Nat Neurosci 2005 8 571 Google Scholar

Haynes, W G Morgan, D A Walsh, S A Mark, A L Sivitz, W I Receptor-mediated regional sympathetic nerve activation by leptin J Clin Invest 1997 100 270 Google Scholar

Bouret, S G Gorski, J N Patterson, C M Hypothalamic neural projections are permanently disrupted in diet-induced obese rats Cell Metab 2008 7 179 Google Scholar

Gorski, J N Dunn-Meynell, A A Levin, B E Maternal obesity increases hypothalamic leptin receptor expression and sensitivity in juvenile obesity-prone rats Am J Physiol Regul Integr Comp Physiol 2007 292 R1782 Google Scholar

Glavas, M M Kirigiti, M A Xiao, X Q Early overnutrition results in early-onset arcuate leptin resistance and increased sensitivity to high-fat diet Endocrinology 2010 151 1598 Google Scholar

Patel, M S Srinivasan, M Metabolic programming due to alterations in nutrition in the immediate postnatal period J Nutr 2010 140 658 Google Scholar

Grayson, B E Levasseur, P R Williams, S M Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet Endocrinology 2010 151 1622 Google Scholar

Vickers, M H Gluckman, P D Coveny, A H The effect of neonatal leptin treatment on postnatal weight gain in male rats is dependent on maternal nutritional status during pregnancy Endocrinology 2008 149 1906 Google Scholar

Yura, S Itoh, H Sagawa, N Role of premature leptin surge in obesity resulting from intrauterine undernutrition Cell Metab 2005 1 371 Google Scholar

Vickers, M H Gluckman, P D Coveny, A H Neonatal leptin treatment reverses developmental programming Endocrinology 2005 146 4211 Google Scholar

Samuelsson, A M Morris, A Igosheva, N Evidence for sympathetic origins of hypertension in juvenile offspring of obese rats Hypertension 2010 55 76 Google Scholar

Samuelsson, A-M Clark, J Shattock, M J Postnatal leptin administration in naїve rat pups leads to leptin resistance, hypertension and gender specific myocardial dysfunction J Dev Orig Health Dis 2 S12

Long, N M Ford, S P Nathanielsz, P W Maternal obesity eliminates the neonatal lamb plasma leptin peak J Physiol 2011 589 1455 Google Scholar

Poston, L Developmental programming and diabetes – the human experience and insight from animal models Best Pract Res Clin Endocrinol Metab 2010 24 541 Google Scholar

Brenneman, D E Rutledge, C O Effect of dietary lipid on locomotor activity and response to psychomotor stimulants Psychopharmacology (Berl) 1982 76 260 Google Scholar

Symonds, M E Sebert, S P Hyatt, M A Budge, H. Nutritional programming of the metabolic syndrome Nat Rev Endocrinol 2009 5 604 Google Scholar

Shelley, P Martin-Gronert, M S Rowlerson, A Altered skeletal muscle insulin signaling and mitochondrial complex II-III linked activity in adult offspring of obese mice Am J Physiol Regul Integr Comp Physiol 2009 297 R675 Google Scholar

Tozuka, Y Kumon, M Wada, E Maternal obesity impairs hippocampal BDNF production and spatial learning performance in young mouse offspring Neurochem Int 2010 57 235 Google Scholar

Fernandes, M Grayton, H Poston, L Prenatal exposure to maternal obesity leads to hyperactivity in offspring Molecular Psychiatry 2011 Google Scholar

Zambrano, E Martinez-Samayoa, P M Rodriguez-Gonzalez, G L Nathanielsz, P W Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats J Physiol 2010 588 1791 Google Scholar

Sen, S Simmons, R A Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats Diabetes 2010 59 3058 Google Scholar

Yan, X Huang, Y Zhao, J X Maternal obesity-impaired insulin signaling in sheep and induced lipid accumulation and fibrosis in skeletal muscle of offspring Biol Reprod 2011 85 172 Google Scholar

Suter, M Bocock, P Showalter, L Epigenomics: maternal high-fat diet exposure in utero disrupts peripheral circadian gene expression in nonhuman primates FASEB J 2011 25 714 Google Scholar

Bruce, K D Cagampang, F R Argenton, M Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression Hepatology 2009 50 1796 Google Scholar

Oken, E Rifas-Shiman, S L Field, A E Frazier, A L Gillman, M W Maternal gestational weight gain and offspring weight in adolescence Obstet Gynecol 2008 112 999 Google Scholar

Wen, X Triche, E W Hogan, J W Shenassa, E D Buka, S L Prenatal factors for childhood blood pressure mediated by intrauterine and/or childhood growth? Pediatrics 127 e713

Wang, J Ma, H Tong, C Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart FASEB J 2010 24 2066 Google Scholar

Huang, Y Yan, X Zhao, J X Maternal obesity induces fibrosis in fetal myocardium of sheep Am J Physiol Endocrinol Metab 2010 299 e968 Google Scholar

Rahmouni, K Morgan, D A Morgan, G M Mark, A L Haynes, W G Role of selective leptin resistance in diet-induced obesity hypertension Diabetes 2005 54 2012 Google Scholar

Dodd, J M Grivell, R M Crowther, C A Robinson, J S Antenatal interventions for overweight or obese pregnant women: a systematic review of randomised trials BJOG 117 1316

Igosheva, N Abramov, A Y Poston, L Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes PLoS One 2010 5 e10074 Google Scholar

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10 - Influences of maternal obesity on the health of the offspring: a review of animal models

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