Developmental Origins Of Obesity Research Articles

Beyond Diet and Exercise: The Impact of Gut Microbiota on Control of Obesity.

Obesity, a widespread health concern characterized by the excessive accumulation of body fat, is a complex condition influenced by genetics, environment, and social determinants. Recent research has increasingly focused on the role of gut microbiota in obesity, highlighting its pivotal involvement in various metabolic processes. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, interacts with the host in a myriad of ways, impacting energy metabolism, appetite regulation, inflammation, and the gut-brain axis. Dietary choices significantly shape the gut microbiota, with diets high in fat and carbohydrates promoting the growth of harmful bacteria while reducing beneficial microbes. Lifestyle factors, like physical activity and smoking, also influence gut microbiota composition. Antibiotics and medications can disrupt microbial diversity, potentially contributing to obesity. Early-life experiences, including maternal obesity during pregnancy, play a vital role in the developmental origins of obesity. Therapeutic interventions targeting the gut microbiota, including prebiotics, probiotics, fecal microbiota transplantation, bacterial consortium therapy, and precision nutrition, offer promising avenues for reshaping the gut microbiota and positively influencing weight regulation and metabolic health. Clinical applications of microbiota-based therapies are on the horizon, with potential implications for personalized treatments and condition-based interventions. Emerging technologies, such as next-generation sequencing and advanced bioinformatics, empower researchers to identify specific target species for microbiota-based therapeutics, opening new possibilities in healthcare. Despite the promising outlook, microbiota-based therapies face challenges related to microbial selection, safety, and regulatory issues. However, with ongoing research and advances in the field, these challenges can be addressed to unlock the full potential of microbiota-based interventions.

Maternal obesity, pregnancy weight gain, and birth weight and risk of colorectal cancer

ObjectiveColorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Obesity is a well-established risk factor for CRC, and fetal or developmental origins of obesity may underlie its effect...

Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring.

Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS's components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.

Food insecurity as a driver of obesity in humans: The insurance hypothesis.

Integrative explanations of why obesity is more prevalent in some sectors of the human population than others are lacking. Here, we outline and evaluate one candidate explanation, the insurance hypothesis (IH). The IH is rooted in adaptive evolutionary thinking: The function of storing fat is to provide a buffer against shortfall in the food supply. Thus, individuals should store more fat when they receive cues that access to food is uncertain. Applied to humans, this implies that an important proximate driver of obesity should be food insecurity rather than food abundance per se. We integrate several distinct lines of theory and evidence that bear on this hypothesis. We present a theoretical model that shows it is optimal to store more fat when food access is uncertain, and we review the experimental literature from non-human animals showing that fat reserves increase when access to food is restricted. We provide a meta-analysis of 125 epidemiological studies of the association between perceived food insecurity and high body weight in humans. There is a robust positive association, but it is restricted to adult women in high-income countries. We explore why this could be in light of the IH and our theoretical model. We conclude that although the IH alone cannot explain the distribution of obesity in the human population, it may represent a very important component of a pluralistic explanation. We also discuss insights it may offer into the developmental origins of obesity, dieting-induced weight gain, and anorexia nervosa.

Metabolomics in the developmental origins of obesity and its cardiometabolic consequences.

In this review, we discuss the potential role of metabolomics to enhance understanding of obesity-related developmental origins of health and disease (DOHaD). We first provide an overview of common techniques and analytical approaches to help interested investigators dive into this relatively novel field. Next, we describe how metabolomics may capture exposures that are notoriously difficult to quantify, and help to further refine phenotypes associated with excess adiposity and related metabolic sequelae over the life course. Together, these data can ultimately help to elucidate mechanisms that underlie fetal metabolic programming. Finally, we review current gaps in knowledge and identify areas where the field of metabolomics is likely to provide insights into mechanisms linked to DOHaD in human populations.

Gene-environment interactions controlling energy and glucose homeostasis and the developmental origins of obesity.

Obesity and type 2 diabetes mellitus (T2DM) often occur together and affect a growing number of individuals in both the developed and developing worlds. Both are associated with a number of other serious illnesses that lead to increased rates of mortality. There is likely a polygenic mode of inheritance underlying both disorders, but it has become increasingly clear that the pre- and postnatal environments play critical roles in pushing predisposed individuals over the edge into a disease state. This review focuses on the many genetic and environmental variables that interact to cause predisposed individuals to become obese and diabetic. The brain and its interactions with the external and internal environment are a major focus given the prominent role these interactions play in the regulation of energy and glucose homeostasis in health and disease.

The association of birth weight and infant growth with physical fitness at 8-9 years of age--the ABCD study.

Low birth weight and accelerated infant growth are independently associated with childhood obesity. We hypothesized that birth weight and infant growth are associated with physical fitness in childhood, and thereby could act as a link in the developmental origins of obesity. In addition, we assessed whether these associations were mediated by fat-free mass (FFM), moderate-to-vigorous physical activity (MVPA) or sedentary behavior (SB). We assessed physical fitness in 194 children of Dutch ethnicity aged 8.6 (±0.35) years from the ABCD cohort. Aerobic fitness was assessed using the 20-meter multistage shuttle run test (20-m MSRT), and neuromuscular fitness using the standing broad jump (SBJ) test and hand grip strength test. MVPA and SB were measured by accelerometry, and FFM by bioelectrical impedance analysis. Low birth weight was defined as below the 10th percentile and accelerated infant growth as an s.d. score weight gain of >0.67 between birth and 12 months. Children with low birth weight and subsequent accelerated infant growth attained a lower 20-m MSRT score than the remainder of the cohort, adjusted for multiple confounders (P<0.01). Birth weight and infant growth were both independently positively associated with hand grip strength, but not after adjusting for current height and body mass index. There was no association of birth weight or infant growth with SBJ. FFM mediated >75% of the association of birth weight and infant growth with hand grip strength, but FFM, MVPA and SB did not mediate the associations with 20-m MSRT. Our results indicate that low birth weight and accelerated infant growth might negatively affect childhood aerobic and neuromuscular fitness. Differences in FFM largely explain the developmental origins of neuromuscular fitness. Consequently impaired fitness may constitute a link between low birth weight, accelerated infant growth and obesity. Hence, optimization of fitness in these children may affect their obesity and cardiovascular disease risk.

Early growth and obesity risk - What should health professionals be advising?

Obesity rates in the UK have been continuously increasing among adults and children and have been attributed to nutritional and lifestyle practices that promote a positive shift in energy balance. Over the last few decades, a growing body of evidence suggests that the origins of obesity start at the earliest stages of human development and specifically pre-conception, in utero and during early infancy. Maternal nutritional status and early life feeding have been identified as ‘critical windows’ for obesity risk. Pre-conception and pregnancy overweight and obesity, as well as fetal exposure to diabetes and hyperglycaemia, have been associated with high birthweight, which, in turn, has been reported to have a direct link with obesity risk later in life. A number of studies have also demonstrated low birthweight to be associated with increased risk of obesity and suggested that low-birthweight term infants who demonstrate early ‘catch-up’ growth have a tendency to become obese adults. Low birthweight has been associated with pre-conception underweight and inadequate in utero nutrition. Although the links between early growth and later obesity risk implicate maternal pre-natal nutrition, it has been suggested that nutrition during early infancy also affects later body composition. Breastfeeding has been associated with a reduced prevalence of obesity, although the evidence is still inconsistent and somewhat limited. Recent advances in the ability to manipulate infant formula composition by reducing its protein content and bringing its composition closer to that of breastmilk could potentially help prevent the rapid weight gain observed in formula-fed infants. Early introduction of complementary foods has also been associated with increased obesity risk later in life. Unfortunately to date, the majority of evidence on the developmental origins of obesity comes from observational studies, making their interpretation difficult and providing an uncertain basis for practice. However, a number of modifiable risk factors in the pre-natal and early post-natal periods of human development have been identified, as well as vulnerable subgroups within the population to these risk factors, which may guide health professionals when advising women regarding lifestyle strategies to reduce the risk of obesity for their offspring and for future generations.

An examination of maternal contributors and potential modifiers of fetal growth in pregnancy

A greater understanding of critical periods of body weight regulation, including pregnancy, may aid in efforts to optimize weight management strategies for the mother and her baby. The gestational period has been implicated to play, in the child, a vital role in the developmental origins of obesity and other cardiometabolic diseases later in life. Therefore, we initially examined existing literature on the role of maternal obesity and its link to pediatric obesity and documented the known underlying physiological mechanisms responsible for this relationship, while suggesting potential intervention targets that may improve maternal–fetal outcomes. In a second paper, we aimed to quantify maternal predictors of large for gestational-age neonates in the Ottawa and Kingston birth cohort with specific hypotheses verifying the independent contribution of maternal prepregnancy body mass index (BMI) and excessive gestational weight gain (GWG) to fetal overgrowth. This paper also highlighted the clinical utility of the revised 2009 Institute of Medicine GWG guidelines and discussed the potential role of physiological factors underlying the observed associations. As follow-ups to our population-level analysis, papers 3 and 4 highlighted how the insulin-like growth factor (IGF) axis, a vital regulator of growth and development, may be compromised at the molecular level in cases of maternal obesity (paper 3) and excessive GWG (paper 4). In paper 3, we showed that maternal obesity is associated with attenuated expression of IGF binding protein-4 (IGFBP-4) in umbilical cord blood and discussed how this may preferentially promote fetal adipogenesis. The effects of excessive GWG on IGF axis protein expression were addressed in paper 4, where we showed that independent of prepregnancy BMI, excessive weight gain during pregnancy is associated with increased expression of IGFBP-3 in maternal circulation in normoglycemic term pregnancies. In that paper we discussed the potential inhibitory role of IGFBP-3 on adipogenesis and how it relates to glucose intolerance during pregnancy. Recognizing that both obesity and excessive GWG can alter physiological processes in a mother and her baby, we concluded that appropriate evidence-based interventions are warranted to best optimize outcomes. In paper 5, we discussed the results of a study that sought to assess patient information channels and knowledge of nutrition and physical activity during pregnancy. The intent was that these findings be applied to best-design efficacious strategies that cater to the needs of our target group of pregnant women. In our analysis we showed that the majority of pregnant women studied would be willing to participate in a lifestyle intervention for their own personal health and that of their child. Of great interest was the observation that most women were not informed of the importance of pregnancy-specific energy intake, or made aware of their own healthy GWG targets. Additionally, many of the respondents reported that they did not receive information that pertained to appropriate physical activity recommendations, even though the vast majority of participants considered this lifestyle modality to be safe during their pregnancy. Finally, in paper 6 we built on the results of our previous work and evaluated the risks and benefits of physical activity during pregnancy on maternal–fetal outcomes through a review of the literature and noted that engaging in nonsedentary pursuits during gestation may aid in maternal weight regulation, protect against metabolic disorders, and optimize neonatal birth weight and body composition. Overall, the collective nature of the papers presented in this dissertation provides qualitative and quantitative evidence to support not only the complexity of body weight regulation in the mother and her baby, but also highlights potential avenues for intervention that may improve maternal–fetal outcomes during this critical period.

Developmental origins of obesity and type 2 diabetes: molecular aspects and role of chemicals

Obesity is a leading risk factor for impaired glucose tolerance and type 2 diabetes (T2D). Although the cause of the obesity epidemic is multi-factorial and not entirely clear, the recent acceleration in incidence is too rapid to be accounted for only by genetics, the wide availability of calorie-rich foods, and increasingly sedentary lifestyles. Accumulating data suggest that the important causes of the obesity epidemic may be related to developmental and early life environmental conditions. The concept of the developmental origins of health and disease (DOHaD) suggests that adverse influences early in development, particularly during intrauterine life, may result in permanent changes in the physiology and metabolism of the infant, which in turn result in an increased risk of non-communicable diseases in adulthood. For example, undernutrition during pregnancy and rapid postnatal weight gain are associated with obesity and T2D in the adult offspring. Moreover, increasing evidence suggests that early-life exposure to a wide range of chemicals has a significant impact on the causes of metabolic disorders. Although the underlying molecular mechanisms remain to be determined, these factors can affect epigenetic processes, such as DNA methylation, allowing the developmental environment to modulate gene transcription. The objective of this review article was to summarize recent progress in the biomedical implications of the DOHaD concept, focusing on the pathogenesis of obesity and T2D, and to discuss a future direction for preventive strategies from a public health perspective.

Developmental origins of obesity and non-communicable disease

Developmental origins of obesity and non-communicable disease

Developmental Origins of Obesity: Programmed Adipogenesis

The metabolic syndrome epidemic, including a marked increase in the prevalence of obesity and gestational diabetes mellitus (GDM) among pregnant women, represents a significant public health problem. There is increasing recognition that the risk of adult obesity is clearly influenced by prenatal and infant environmental exposures, particularly nutrition. This tenet is the fundamental basis of developmental programming. Low birth weight, together with infant catch-up growth, is associated with a significant risk of adult obesity. Exposure to maternal obesity, with or without GDM, or having a high birth weight also represents an increased risk for childhood and adult obesity. Animal models have replicated human epidemiologic findings and elucidated potential programming mechanisms that include altered organ development, cellular signaling responses, and epigenetic modifications. Prenatal care has made great strides in optimizing maternal, fetal, and neonatal health, and now has the opportunity to begin interventions which prevent or reduce childhood/adult obesity. Guidelines that integrate optimal pregnancy nutrition and weight gain, management of GDM, and newborn feeding strategies with long-term consequences on adult obesity, remain to be elucidated.

Can exercise prevent coronary artery disease even on a high fat diet?

Can exercise prevent coronary artery disease even on a high fat diet?

Developmental origins of obesity: Early feeding environments, infant growth, and the intestinal microbiome

Pediatric overweight and obesity are growing problems worldwide, with increasing prevalence among even infants and young children. The refractory nature of early overweight necessitates identifying the factors contributing to early excess weight gain for successful intervention. Early feeding practices may be particularly important in shaping long-term vulnerability to obesity. How and what infants are fed can influence weight gain, adiposity, and energy metabolism during infancy and across the life course through a number of interacting physiological and behavioral pathways. This article argues that these biological mechanisms interact with the social and behavioral context of infant feeding to create differential vulnerability to later obesity. This article reviews recent research on the potential mechanisms linking infant feeding and risk of later obesity, focusing on the emerging role of microflora colonization. The nutritive and non-nutritive components of breastmilk, formula and solid foods and the practices surrounding feeding shape the infant metabolome, programming growth rates and body composition, altering metabolism and physiology, promoting differential microfloral colonization, and shaping behavioral responses to foods and eating. The occurrence of chronic disease precursors at increasingly younger ages and the tendency of overweight young children to become overweight adolescents and adults underscore the importance of understanding this complex early exposure and intervening early to prevent the development of obesity in increasingly weight-promoting environments.

Hruschka et al. Respond

We thank Dr. Bartle for pointing out that clustering of obesity in families would be expected given shared genetics. Of course, we would also expect that common home environment plays a role.1 Our key finding that shared social norms only weakly account for shared body size in a sample including both family and friends leaves room for developing a number of plausible alternative hypotheses for the social bases of obesity clustering, including some that more directly take into account genetics. But as obesity has demonstrated high heritability and a large norm of reaction, we would expect that the most ultimately satisfying answers must be focused on interactions between relevant genetic pathways and the physical and social environment. We are especially encouraged in this regard by recent findings on the developmental origins of obesity,2 interactions between feeding environment and genetic risk,3 and genetic influences on how people construct their social environments.4 A direct focus on mechanisms—whether by examining how body size ideals influence behavior or by mapping specific genetic pathways—will be the crucial step in understanding how and why the social environment matters to the obesity epidemic.

Prediction of fat-free mass and percentage of body fat in neonates using bioelectrical impedance analysis and anthropometric measures: validation against the PEA POD

Accurate assessment of neonatal body composition is essential to studies investigating neonatal nutrition or developmental origins of obesity. Bioelectrical impedance analysis or bioimpedance analysis is inexpensive, non-invasive and portable, and is widely used in adults for the assessment of body composition. There are currently no prediction algorithms using bioimpedance analysis in neonates that have been directly validated against measurements of fat-free mass (FFM). The aim of the study was to evaluate the use of bioimpedance analysis for the estimation of FFM and percentage of body fat over the first 4 months of life in healthy infants born at term, and to compare these with estimations based on anthropometric measurements (weight and length) and with skinfolds. The present study was an observational study in seventy-seven infants. Body fat content of infants was assessed at birth, 6 weeks, 3 and 4·5 months of age by air displacement plethysmography, using the PEA POD body composition system. Bioimpedance analysis was performed at the same time and the data were used to develop and test prediction equations for FFM. The combination of weight+sex+length predicted FFM, with a bias of < 100 g and limits of agreement of 6-13 %. Before 3 months of age, bioimpedance analysis did not improve the prediction of FFM or body fat. At 3 and 4·5 months, the inclusion of impedance in prediction algorithms resulted in small improvements in prediction of FFM, reducing the bias to < 50 g and limits of agreement to < 9 %. Skinfold measurements performed poorly at all ages.

Lifecourse infectious origins of sexual inequalities in central adiposity

Social disparities in obesity are often more marked among women than men, possibly due to social factors. Taking a life-history perspective, we hypothesized that childhood infections could be relevant via sex-specific effects of immune system activation on sexual development and, hence, body shape. We used multivariable linear regression to assess the sex-specific, adjusted associations of 'childhood' pathogens [0 (n = 1002), 1 (n = 2199), 2 (n = 3442) or 3 (n = 4833) of HSV1, CMV and hepatitis A antibodies] and 'adult' pathogens [0 (n = 5836), 1 (n = 3018) or ≥ 2 (n = 720) of HSV2, HHV8 and hepatitis B or C) with waist-hip ratio (WHR) and body mass index (BMI) standard deviations (SDs) using NHANES III (1988-94). As validation, we assessed associations with height. 'Childhood' pathogens were positively associated with WHR among women [0.18 SD, 95% confidence interval (95% CI) 0.04-0.32 for 3, compared with 0], but not men (-0.04 SD, 95% CI -0.15 to 0.08), adjusted for age, education, race/ethnicity, smoking and alcohol. Further adjustments for leg length barely changed the estimates. There were no such sex-specific associations for BMI or for adult pathogens. 'Childhood', but not 'adult', pathogens were negatively associated with height, adjusted for age, sex, education and race/ethnicity. These observations are consistent with the lifecourse hypothesis that early exposure to infections makes women vulnerable to central obesity. This hypothesis potentially sheds new light on the developmental origins of obesity, and is consistent with the generally higher levels of central obesity among women than men in developing populations.

Developmental Origins of Obesity - Genetic and Epigenetic Determinants

Background: Childhood obesity is a major public health concern. The importance of genes in development of obesity is evident from twin and family studies. Moreover, epigenetic events in early life may play an important role in obesity etiology. Aim: We aimed to outline and discuss the role of genetic and epigenetic influences on development of obesity in early life from around birth and into adolescence. Methods: We included a series of interesting contributions on the area. First, the topic was addressed on the relative influence of genes and environment. Next, we turned to the significance of epigenetic events. Results: Genetic influences play an important role in individual differences in body fatness throughout childhood and adolescence, with an increasing heritability with age. In addition, environmental factors can influence the epigenetic regulation, making the individual more susceptible to develop obesity. Conclusion: Our knowledge of genetic and epigenetic contributions to obesity development has increased dramatically during the last century. Future studies and technological advnces, will undoubtedly reveal even more complicated pathways that have to be considered when trying to prevent the dramatic worldwide increase in obesity.

Neonatal Exposure to Leptin Augments Diet‐induced Obesity in Leptin‐deficient Ob/Ob Mice

Epidemiological evidence has revealed that undernutrition in utero is closely associated with obesity and related detrimental metabolic sequelae in adulthood. Recently, using a wild-type (wt) mouse model in which offspring were exposed to intrauterine undernutrition (UN offspring), we reported that the premature leptin surge during neonatal growth promotes lifelong changes in energy regulating circuitry in the hypothalamus, thus playing an important role in the development of pronounced obesity on a high-fat diet (HFD) in adulthood. Here, we further evaluate the essential involvement of leptin in the developmental origins of obesity using leptin-deficient ob/ob mice. We assessed the progression of obesity on an HFD in adult leptin-deficient ob/ob male mice that were exposed to intrauterine undernutrition by maternal food restriction (ob/ob UN offspring) or to leptin treatment during the neonatal period; this treatment is comparable to the premature leptin surge observed in the wt-UN offspring. On an HFD, the body weight of the male ob/ob UN offspring paralleled that of the ob/ob offspring exposed to normal intrauterine nutrition (ob/ob NN offspring). In contrast, early exposure to leptin in the ob/ob NN offspring during early neonatal growth reproduced the development of pronounced obesity on an HFD in adulthood. The presence of leptin and associated energy regulation are indispensable in the acceleration of obesity on an HFD caused by undernutrition in utero. The premature leptin surge plays an essential role in the developmental origins of obesity as a programming signal during the early neonatal period.

The developmental origins of obesity

The developmental origins of obesity