Early life influences on obesity risk: maternal overnutrition and programming of obesity

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.

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Developmental and Intergenerational Landscape of Human Circulatory Lipidome and its Association with Obesity Risk

10.1101/2021.04.23.437677 ◽

2021 ◽

Author(s):

Sartaj Ahmad Mir ◽

Li Chen ◽

Satvika Burugupalli ◽

Bo Burla ◽

Shanshan Ji ◽

...

Keyword(s):

Cord Blood ◽

Human Health ◽

Lipid Composition ◽

Early Life ◽

Vital Role ◽

Obesity Risk ◽

Maternal Circulation ◽

Lipid Species ◽

Health And Development ◽

Maternal Adiposity

AbstractLipids play a vital role in human health and development, but changes to their circulatory levels during gestation and in early life are poorly understood. Here we present the first developmental and intergenerational landscape of the human circulatory lipidome, derived by profiling of 480 lipid species representing 25 lipid classes, in mothers and their offspring (n=2491). Levels of 66% of the profiled lipids increased in maternal circulation during gestation, while cord blood had higher concentrations of acylcarnitines and lysophospholipids. The offspring lipidome at age six years revealed striking similarities with postnatal maternal lipidome (adult) in its lipid composition and concentrations. Comparison of lipids associated with child and maternal adiposity identified a 92% overlap, implying intergenerational similarities in the lipid signatures of obesity risk. We also catalogued lipid signatures linked with maternal adiposity during gestation and offspring birthweight, and validated (>70% overlap) the findings in an independent birth-cohort (n=1935).

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A Practical Screening Tool to Predict Early Childhood Obesity Risk: Examining a Birth Cohort

Clinical Pediatrics ◽

10.1177/0009922820971006 ◽

2020 ◽

pp. 000992282097100

Author(s):

James Gannon ◽

Allison J. Pollock ◽

David B. Allen ◽

Pamela J. Kling

Keyword(s):

Risk Factors ◽

Childhood Obesity ◽

Iron Deficiency ◽

Birth Cohort ◽

Early Life ◽

Maternal Obesity ◽

Maternal Diabetes ◽

Large For Gestational Age ◽

Obesity Risk ◽

Total Risk

Children obese at the age of 5 years are at greater risk of lifelong obesity. Because certain risks of obesity can be identified in early infancy, a tool for obesity risk prediction in early life would be clinically useful. We investigated predictors of obesity risk in a novel, prospectively collected healthy birth cohort recruited for demographic risks to develop iron deficiency at 1 year, a cohort leveraged because risk factors for iron deficiency and obesity overlap. Obesity at the age of 5 years was defined as age- and sex-specific body mass index Z-score ( zBMI) >2SD. For each child, obesity risk factors were summed. Of 10 total risk factors, the following 4 key risks were identified: maternal obesity, maternal diabetes, large for gestational age, or breastfeeding <6 months. Childhood obesity was predicted by either ≥3 total number of risks ( P < .033), any key risk ( P < .002), or summing key risks ( P < .0001). In clinical practice, summing early life risk factors may be a useful strategy for preemptive counseling.

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Milk Feeding, Solid Feeding, and Obesity Risk: A Review of the Relationships Between Early Life Feeding Practices and Later Adiposity

Current Obesity Reports ◽

10.1007/s13679-012-0034-7 ◽

2012 ◽

Vol 2 (1) ◽

pp. 58-64 ◽

Cited By ~ 4

Author(s):

Claire Farrow ◽

Emma Haycraft ◽

Gemma Mitchell

Keyword(s):

Early Life ◽

Feeding Practices ◽

Obesity Risk ◽

Milk Feeding

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Early life exposure to antibiotics and acid suppressants increases obesity risk

Clinical Pharmacist ◽

10.1211/cp.2018.20205890 ◽

2018 ◽

Keyword(s):

Early Life ◽

Obesity Risk ◽

Early Life Exposure

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

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2018.0116 ◽

2019 ◽

Vol 374 (1770) ◽

pp. 20180116 ◽

Cited By ~ 10

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’.

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

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0029 ◽

2013 ◽

Vol 15 (1) ◽

Cited By ~ 2

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.

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