scholarly journals Maternal Obesity and Developmental Programming of Metabolic Disorders in Offspring: Evidence from Animal Models

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
M. Li ◽  
D. M. Sloboda ◽  
M. H. Vickers
Keyword(s):  
Animal Models ◽  
Early Life ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
Maternal Weight ◽  
Critical Window ◽  
Obesity Epidemic ◽  
Obesity And Overweight ◽  
Increased Risk ◽  
Maternal Overnutrition

The incidence of obesity and overweight has reached epidemic proportions in the developed world as well as in those countries transitioning to first world economies, and this represents a major global health problem. Concern is rising over the rapid increases in childhood obesity and metabolic disease that will translate into later adult obesity. Although an obesogenic nutritional environment and increasingly sedentary lifestyle contribute to our risk of developing obesity, a growing body of evidence links early life nutritional adversity to the development of long-term metabolic disorders. In particular, the increasing prevalence of maternal obesity and excess maternal weight gain has been associated with a heightened risk of obesity development in offspring in addition to an increased risk of pregnancy-related complications. The mechanisms that link maternal obesity to obesity in offspring and the level of gene-environment interactions are not well understood, but the early life environment may represent a critical window for which intervention strategies could be developed to curb the current obesity epidemic. This paper will discuss the various animal models of maternal overnutrition and their importance in our understanding of the mechanisms underlying altered obesity risk in offspring.

scholarly journals Pregnancy, obesity and insulin resistance: maternal overnutrition and the target windows of fetal development

2013 ◽  
Vol 15 (1) ◽  
Author(s):  
Beverly S. Muhlhausler ◽  
Jessica R. Gugusheff ◽  
Zhi Yi Ong ◽  
Mini A. Vithayathil
Keyword(s):  
Insulin Resistance ◽  
Early Life ◽  
Maternal Obesity ◽  
Nutrient Supply ◽  
Personal Perspective ◽  
Human Populations ◽  
Maternal Undernutrition ◽  
Increased Risk ◽  
Maternal Overnutrition ◽  
The Impact

AbstractA substantial body of literature has demonstrated that the nutritional environment an individual experiences before birth or in early infancy is a key determinant of their health outcomes across the life course. This concept, the developmental origins of health and disease (DOHaD) hypothesis, was initially focused on the adverse consequences of exposure to a suboptimal nutrient supply and provided evidence that maternal undernutrition, fetal growth restriction, and low birth weight were associated with heightened risk of central adiposity, insulin resistance, and cardiovascular disease. More recently, the epidemic rise in the incidence of maternal obesity has seen the attention of the DOHaD field turn toward identifying the impact on the offspring of exposure to an excess nutrient supply in early life. The association between maternal obesity and increased risk of obesity in the offspring has been documented in human populations worldwide, and animal models have provided critical insights into the biological mechanisms that drive this relationship. This review will discuss the important roles that programming of the adipocyte and programming of the central neural networks which control appetite and reward play in the early life programming of metabolic disease by maternal overnutrition. It will also highlight the important research gaps and challenges that remain to be addressed and provide a personal perspective on where the field should be heading in the coming 5–10 years.

The impact of early life gut colonization on metabolic and obesogenic outcomes: what have animal models shown us?

2015 ◽  
Vol 7 (1) ◽  
pp. 15-24 ◽  
Author(s):  
J. G. Wallace ◽  
W. Gohir ◽  
D. M. Sloboda
Keyword(s):  
Animal Models ◽  
Gut Microbiota ◽  
Early Life ◽  
Maternal Obesity ◽  
Communicable Disease ◽  
Critical Periods ◽  
Early Life Adversity ◽  
Gut Colonization ◽  
Increased Risk ◽  
The Impact

The rise in the occurrence of obesity to epidemic proportions has made it a global concern. Great difficulty has been experienced in efforts to control this growing problem with lifestyle interventions. Thus, attention has been directed to understanding the events of one of the most critical periods of development, perinatal life. Early life adversity driven by maternal obesity has been associated with an increased risk of metabolic disease and obesity in the offspring later in life. Although a mechanistic link explaining the relationship between maternal and offspring obesity is still under investigation, the gut microbiota has come forth as a new factor that may play a role modulating metabolic function of both the mother and the offspring. Emerging evidence suggests that the gut microbiota plays a much larger role in mediating the risk of developing non-communicable disease, including obesity and metabolic dysfunction in adulthood. With the observation that the early life colonization of the neonatal and postnatal gut is mediated by the perinatal environment, the number of studies investigating early life gut microbial establishment continues to grow. This paper will review early life gut colonization in experimental animal models, concentrating on the role of the early life environment in offspring gut colonization and the ability of the gut microbiota to dictate risk of disease later in life.

scholarly journals Maternal Overnutrition Induces Long-Term Cognitive Deficits across Several Generations

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 7 ◽  
Author(s):  
Gitalee Sarker ◽  
Daria Peleg-Raibstein
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Deficits ◽  
Maternal Obesity ◽  
Cognitive Impairments ◽  
Long Term Effects ◽  
Ample Evidence ◽  
Increased Risk ◽  
Maternal Overnutrition

Ample evidence from epidemiological studies has linked maternal obesity with metabolic disorders such as obesity, cardiovascular disease, and diabetes in the next generation. Recently, it was also shown that maternal obesity has long-term effects on the progeny’s central nervous system. However, very little is known regarding how maternal overnutrition may affect, in particular, the cognitive abilities of the offspring. We reported that first-generation offspring exposed to a maternal high-fat diet (MHFD) displayed age-dependent cognitive deficits. These deficits were associated with attenuations of amino acid levels in the medial prefrontal cortex and the hippocampus regions of MHFD offspring. Here, we tested the hypothesis that MHFD in mice may induce long-term cognitive impairments and neurochemical dysfunctions in the second and third generations. We found that MHFD led to cognitive disabilities and an altered response to a noncompetitive receptor antagonist of the N-Methyl-D-aspartic acid (NMDA) receptor in adult MHFD offspring in both second and third generations in a sex-specific manner. Our results suggest that maternal overnutrition leads to an increased risk of developing obesity in subsequent generations as well as to cognitive impairments, affecting learning and memory processes in adulthood. Furthermore, MHFD exposure may facilitate pathological brain aging which is not a consequence of obesity. Our findings shed light on the long-term effects of maternal overnutrition on the development of the central nervous system and the underlying mechanisms which these traits relate to disease predisposition.

scholarly journals Effects of a Lifestyle Intervention in Routine Care on Short- and Long-Term Maternal Weight Retention and Breastfeeding Behavior—12 Months Follow-up of the Cluster-Randomized GeliS Trial

2019 ◽  
Vol 8 (6) ◽  
pp. 876 ◽  
Author(s):  
Julia Hoffmann ◽  
Julia Günther ◽  
Lynne Stecher ◽  
Monika Spies ◽  
Dorothy Meyer ◽  
...  
Keyword(s):  
Lifestyle Intervention ◽  
Exclusive Breastfeeding ◽  
Maternal Obesity ◽  
Routine Care ◽  
Control Group ◽  
Weight Retention ◽  
Maternal Weight ◽  
Increased Risk ◽  
Postpartum Weight ◽  
Cluster Randomized

Postpartum weight retention (PPWR) is associated with an increased risk for maternal obesity and is discussed to be influenced by breastfeeding. The objective was to evaluate the effect of a lifestyle intervention delivered three times during pregnancy and once in the postpartum period on PPWR and on maternal breastfeeding behavior. In total, 1998 participants of the cluster-randomized “healthy living in pregnancy” (GeliS) trial were followed up until the 12th month postpartum (T2pp). Data were collected using maternity records and questionnaires. Data on breastfeeding behavior were collected at T2pp. At T2pp, mean PPWR was lower in women receiving counseling (IV) compared to the control group (C) (−0.2 ± 4.8 kg vs. 0.6 ± 5.2 kg), but there was no significant evidence of between-group differences (adjusted p = 0.123). In the IV, women lost more weight from delivery until T2pp compared to the C (adjusted p = 0.008) and showed a slightly higher rate of exclusive breastfeeding (IV: 87.4%; C: 84.4%; adjusted p < 0.001). In conclusion, we found evidence for slight improvements of maternal postpartum weight characteristics and the rate of exclusive breastfeeding in women receiving a lifestyle intervention embedded in routine care, although the clinical meaning of these findings is unclear.

scholarly journals Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic review

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252343
Author(s):  
Gitte Hedermann ◽  
Paula L. Hedley ◽  
Ida N. Thagaard ◽  
Lone Krebs ◽  
Charlotte Kvist Ekelund ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Gestational Diabetes ◽  
Cohort Studies ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
Heart Defects ◽  
Increased Risk ◽  
Maternal Overweight

Background Congenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors. Methods A systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score. Results Of the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes. Conclusions Future studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanisms of metabolic disorders, present during pregnancy, and their association, both as single conditions and–particularly–in combination, with CHDs are needed.

scholarly journals Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Minglan Li ◽  
Clare M. Reynolds ◽  
Stephanie A. Segovia ◽  
Clint Gray ◽  
Mark H. Vickers
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Early Life ◽  
Fatty Liver Disease ◽  
Maternal Obesity ◽  
Later Life ◽  
Developmental Programming ◽  
Nonalcoholic Fatty Liver ◽  
Increased Risk

Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common liver disease globally and parallels rising obesity rates. The developmental origins of health and disease hypothesis have linked alterations in the early life environment to an increased risk of metabolic disorders in later life. Altered early life nutrition, in addition to increasing risk for the development of obesity, type 2 diabetes, and cardiovascular disease in offspring, is now associated with an increased risk for the development of NAFLD. This review summarizes emerging research on the developmental programming of NAFLD by both maternal obesity and undernutrition with a particular focus on the possible mechanisms underlying the development of hepatic dysfunction and potential strategies for intervention.

scholarly journals Early life programming in mice by maternal overnutrition: mechanistic insights and interventional approaches

2019 ◽  
Vol 374 (1770) ◽  
pp. 20180116 ◽  
Author(s):  
Lisa M. Nicholas ◽  
Susan E. Ozanne
Keyword(s):  
Early Life ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
Evolutionary Medicine ◽  
Early Life Programming ◽  
Effective Interventions ◽  
Human Situation ◽  
Pregnancy And Lactation ◽  
Maternal Overnutrition ◽  
Offspring Health

Animal models have been indispensable in elucidating the potential causative mechanisms underlying the effects of maternal diet on offspring health. Of these, the mouse has been widely used to model maternal overnutrition and/or maternal obesity and to study its effects across one or more generations. This review discusses recent findings from mouse models, which resemble the human situation, i.e. overnutrition/obesity across pregnancy and lactation. It also highlights the importance of embryo transfer models in identifying critical developmental period(s) during which specific metabolic changes are programmed in the offspring. The mouse is also an excellent tool for maternal intervention studies aimed at elucidating the longer-term effects on the offspring and for defining possible maternal factors underling the programming of metabolic adversity in offspring. While knowledge of the mouse genome and the molecular tools available have allowed great progress to be made in the field, it is clear that we need to define if the effects on the offspring are mediated by maternal obesity per se or if specific components of the maternal metabolic environment are more important. We can then begin to identify at-risk offspring and to design more effective interventions for the mother and/or her child. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

scholarly journals Identification of blood cell transcriptome‐based biomarkers in adulthood predictive of increased risk to develop metabolic disorders using early life intervention rat models

2020 ◽  
Vol 34 (7) ◽  
pp. 9003-9017 ◽  
Author(s):  
Nara Szostaczuk ◽  
Evert M. Schothorst ◽  
Juana Sánchez ◽  
Teresa Priego ◽  
Mariona Palou ◽  
...  
Keyword(s):  
Blood Cell ◽  
Early Life ◽  
Metabolic Disorders ◽  
Rat Models ◽  
Increased Risk ◽  
Cell Transcriptome

scholarly journals Maternal Obesity, Birth Size, and Risk of Childhood Cancer Development

2019 ◽  
Vol 188 (8) ◽  
pp. 1503-1511 ◽  
Author(s):  
Shaina L Stacy ◽  
Jeanine M Buchanich ◽  
Zhen-qiang Ma ◽  
Christina Mair ◽  
Linda Robertson ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Early Life ◽  
Maternal Obesity ◽  
Birth Certificate ◽  
Cancer Development ◽  
Related Factors ◽  
Early Life Exposure ◽  
Increased Risk ◽  
Development Accounting ◽  
Newborn Size

Abstract Infants and children are particularly vulnerable to in utero and early-life exposures. Thus, a mother’s exposures before and during pregnancy could have important consequences for her child’s health, including cancer development. We examined whether birth certificate–derived maternal anthropometric characteristics were associated with increased risk of subsequent childhood cancer development, accounting for established maternal and infant risk factors. Pennsylvania birth and cancer registry files were linked by the state Department of Health, yielding a virtual cohort of births and childhood cancers from 2003 through 2016. The analysis included 1,827,875 infants (13,785,309 person-years at risk), with 2,352 children diagnosed with any cancer and 747 with leukemia before age 14 years. Children born to mothers with a body mass index (weight (kg)/height (m)2) of ≥40 had a 57% (95% confidence interval: 12, 120) higher leukemia risk. Newborn size of ≥30% higher than expected was associated with 2.2-fold and 1.8-fold hazard ratios for total childhood cancer and leukemia, respectively, relative to those with expected size. Being <30% below expected size also increased the overall cancer risk (P for curvilinearity < 0.0001). Newborn size did not mediate the association between maternal obesity and childhood cancer. The results suggest a significant role of early-life exposure to maternal obesity- and fetal growth–related factors in childhood cancer development.

scholarly journals Association between maternal obesity and metabolic disorders and congenital heart defects in the offspring: a literature review

2020 ◽  
Author(s):  
Gitte Hedermann ◽  
Paula L Hedley ◽  
Ida N Thagaard ◽  
Lone Krebs ◽  
Thorkild IA Sørensen ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
Heart Defects ◽  
Chronic Hypertension ◽  
Mortality And Morbidity ◽  
Increased Risk ◽  
Early Onset Preeclampsia ◽  
The Individual

SummaryCongenital heart defects (CHDs) are the most common congenital malformation and will, in severe cases, have a serious impact on neonatal mortality and morbidity. The aetiology of CHDs is complex. Large cohort studies have reported an association between increased risk of CHDs in the offspring and individual maternal metabolic disorders such as diabetes, hypertension, preeclampsia, and obesity. All conditions that can be related to insulin resistance and possibly metabolic syndrome (MetS). The aim of this review is to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia, and MetS, or combinations thereof and CHDs in the offspring. A literature search was performed using PubMed and Embase databases. Of the 2,076 potentially relevant identified studies, 30 qualified for inclusion. Only one study dealt with the combination of more than one maternal metabolic condition as risk factor for CHDs in the offspring. All other studies investigated the individual metabolic disorders and their association with CHDs. Some disorders (chronic hypertension, gestational diabetes, and obesity) increased risk of CHDs marginally whereas pregestational diabetes and early-onset preeclampsia were highly associated with CHDs. Future studies on the combination of several metabolic disorders in the same pregnancy and their association with CHDs are needed.

Sign in / Sign up

Export Citation Format

Share Document