Maternal nutritional programming of fetal adipose tissue development: Long‐term consequences for later obesity

Abstract

As obesity reaches epidemic levels in the United States there is an urgent need to understand the developmental pathways leading to this condition. Obesity increases the risk of hypertension and diabetes, symptoms of which are being seen with increased incidence in children. Adipocyte development begins in the fetus and, in contrast to all other tissues whose growth ceases in late juvenile life, it has the capacity for "unlimited" growth. In normal healthy individuals, the increase in fat mass with age is accompanied by a parallel increase in cortisol sensitivity, i.e., increased glucocorticoid receptor abundance and increased activity of the enzyme 11beta hydroxysteroid dehydrogenase type 1. Enhanced adipocyte sensitivity to cortisol is promoted in offspring born to mothers that were nutrient-restricted in utero in conjunction with increased peroxisome proliferator activated receptor alpha. This adaptation only appears to be associated with greater fat mass in the offspring when maternal nutrient restriction is confined to late gestation, coincident with the period of maximal fetal growth. In these offspring, increased fat mass is accompanied by glucose intolerance and insulin resistance, in conjunction with an adipose tissue specific reduction in glucose transporter 4 abundance. In conclusion, changes in maternal and, therefore, fetal nutrient supply at specific stages of gestation have the potential to substantially increase the risk of those offspring becoming obese in later life. The extent to which changes in dietary habits, both during pregnancy and in later life, may act to contribute to the current explosion in childhood and adult obesity remains a scientific and public health challenge to us all.

Nutritional programming of gastrointestinal tract development. Is the pig a good model for man?

“…LGA infants may be a consequence of maternal hyperglycaemia in late pregnancy which is not detected by the routine screening test for gestational diabetes mellitus (157) . A study of Japanese newborns found the morbidity rate of newborns excluding idiopathic hyperbilirubinaemia to be 10 %, which increased with gestational age and was accompanied by an increment of birth trauma.…”

Maternal diet, breastfeeding and adolescent body composition: a 16-year prospective study

“…1 Obesity in childhood and adolescence not only leads to increased incidence of hypertension, diabetes and morbidity, but also to adult obesity and its related adverse metabolic and cardiovascular sequelae. 2 Once obesity is established, it may be less amenable to population-based lifestyle interventions than predicted. 3 Adipocyte development begins in the fetus and has the capacity for 'unlimited' growth; 2 thus, exploring the determinants of body composition and understanding which early-life events regulate adipose tissue distribution in offspring are likely to provide important insights for novel interventions that may prevent excess adiposity in later life.…”

Malnutrition and experimental epilepsy

“…22 However, there is a growing body of evidence from epidemiological studies in humans and from controlled investigations in animal models that genome regulation is largely modified by the nutritional environment such as an amount and composition of nutrients available to the offspring during prenatal and neonatal periods. [23][24][25][26][27] There are numerous studies showing that a suboptimal intrauterine environment, as well as suboptimal nutrition during early neonatal life alters development. 22 This situation can predispose the individual to lifelong health problems like metabolic syndrome or related diseases (such as glucose intolerance, insulin resistance, cardiovascular disease, hypertension, and obesity).…”