Pregnancy support- Fetal Programming

Obesity - updated: 03 November 2008

The thrifty phenotype as an adaptive maternal effect

Biol Rev Camb Philos Soc. 2007 Feb;82(1):143-72

Wells JC.

Human diseases in adulthood are increasingly associated with growth patterns in early life, implicating early-life nutrition as the underlying mechanism. The thrifty phenotype hypothesis proposed that early-life metabolic adaptations promote survival, with the developing organism responding to cues of environmental quality by selecting an appropriate trajectory of growth. Recently, some authors have proposed that the thrifty phenotype is also adaptive in the longer-term, by preparing the organism for its likely adult environment. However, windows of plasticity close early during human development, and subsequent environmental changes may result in the selected trajectory becoming inappropriate, leading to adverse effects on health. This paradox generates uncertainty as to whether the thrifty phenotype is indeed adaptive for the offspring in humans. The thrifty phenotype should not be considered a dichotomous concept, rather it refers to the capacity of all offspring to respond to environmental information during early ontogenetic development. This article argues that the thrifty phenotype is the consequence of three different adaptive processes - niche construction, maternal effects, and developmental plasticity - all of which in humans are influenced by our large brains. While developmental plasticity represents an adaptation by the offspring, both niche construction and parental effects are subject to selection on parental rather than offspring fitness. The three processes also operate at different paces. Human offspring do not become net calories-producers until around 18 years of age, such that the high energy costs of the human brain are paid primarily by the mother, even after weaning. The evolutionary expansion of human brain volume occurred in environments characterised by high volatility, inducing strong selective pressure on maternal capacity to provision multiple offspring simultaneously. The thrifty phenotype is therefore best considered as a manipulation of offspring phenotype for the benefit of maternal fitness. The information that enters offspring phenotype during early development does not predict the likely future environment of the offspring, but rather reflects the mother's own developmental experience and the quality of the environment during her own maturation. Offspring growth trajectory thus becomes aligned with long-term maternal capacity to provision. In contemporary populations, the sensitivity of offspring development to maternal phenotype exposes the offspring to adverse effects, through four distinct pathways. The offspring may be exposed to (1) poor maternal metabolic control (e.g. gestational diabetes), (2) maternally derived toxins (e.g. maternal smoking), or (3) low maternal social status (e.g. small size). Adverse consequences of these effects may then be exacerbated by (4) exposure either to the "toxic" western environment in postnatal life, in which diet and physical activity levels are mismatched with metabolic experience in utero, or at the other extreme to famine. The rapid emergence of the epidemic of the metabolic syndrome in the 20th Century reflects the rapid acceleration in the pace of niche construction relative to the slower physiological combination of developmental plasticity and parental effects

Publication Types:

• Review

Fetal and neonatal pathways to obesity

Front Horm Res. 2008;36:61-72

Gluckman PD, Hanson MA, Beedle AS, Raubenheimer D.

Evolutionary and developmental perspectives add considerably to our understanding of the aetiology of obesity and its related disorders. One pathway to obesity represents the maladaptive consequences of an evolutionarily preserved mechanism by which the developing mammal monitors nutritional cues from its mother and adjusts its developmental trajectory accordingly. Prediction of a nutritionally sparse environment leads to a phenotype that promotes metabolic parsimony by favouring fat deposition, insulin resistance, sarcopenia and low energy expenditure. But this adaptive mechanism evolved to accommodate gradual changes in nutritional environment; rapid transition to a situation of high energy density results in a mismatch between predicted and actual environments and increased susceptibility to metabolic disease. This pathway may also explain why breast and bottle feeding confer different risks of obesity. We discuss how early environmental signals act through epigenetic mechanisms to alter metabolic partitioning, glucocorticoid action and neuroendocrine control of appetite. A second pathway involves alterations in fetal insulin levels, as seen in gestational diabetes, leading to increased prenatal fat mass which is subsequently amplified by postnatal factors. Both classes of pathway may coexist in an individual. This developmental approach to obesity suggests that potential interventions will vary according to the target population.

Early growth and adult health outcomes--lessons learned from the Helsinki Birth Cohort Study

Matern Child Nutr. 2005 Jul;1(3):149-54

Eriksson JG.

Slow growth during fetal life and infancy is often followed by accelerated weight gain in childhood. These patterns of growth seem to precede the development of coronary heart disease (CHD) and type 2 diabetes in adult life. Patterns of growth associated with CHD and type 2 diabetes in adult life are described based upon findings from the Helsinki Birth Cohort Study. We are beginning to understand that adult degenerative diseases are associated with different patterns of early growth. Yet it is not clear what optimal growth is and how it can be achieved. Most data suggest that the development of many non-communicable diseases involve a number of interactions including genetic ones. Therefore these diseases can best be focused upon from a life cycle perspective

Publication Types:

• Review

Is later obesity programmed in utero?

Curr Drug Targets. 2007 Aug;8(8):923-34

Vickers MH, Krechowec SO, Breier BH.

The global prevalence of obesity has increased markedly over the last two decades with over 50% of all adults in the UK and USA classified as overweight or obese. Furthermore, the prevalence of obesity in children has risen by over 40% in the last 16 years. Obesity results from the interaction of many factors, including genetic, metabolic, behavioral, and environmental influences. However, the rate at which obesity is increasing suggests that environmental and behavioral influences, rather than genetic changes, have fueled the epidemic. In this context, it is of particular relevance that epidemiological and experimental studies have highlighted a relationship between the periconceptual, fetal and early infant phases of life and the subsequent development of adult adiposity. This relationship; the "developmental origins of health and disease" (DOHaD) model, speculates that the fetus adapts to adverse environmental cues in utero with permanent readjustments in homeostatic systems to aid survival. However, these adaptations, known as predictive adaptive responses, may ultimately be disadvantageous in postnatal life and may lead to an increased risk of chronic non-communicable disease in adulthood. This review summarises recent work in animal models and observations in the clinical and epidemiological settings on the in-utero origins of obesity and related metabolic disorders.

Publication Types:

• Review

Publication Types:

• Review