Maternal nutrition and risk of obesity in offspring: the Trojan horse of developmental plasticity

Abstract

Mammalian embryos have evolved to adjust their organ and tissue development in response to an atypical environment. This adaptation, called phenotypic plasticity, allows the organism to thrive in the anticipated environment in which the fetus will emerge. Barker and colleagues proposed that if the environment in which the fetus emerges differs from that in which it develops, phenotypic plasticity may provide an underlying mechanism for disease. Epidemiological studies have shown that humans born small- or large-for-gestational-age, have a higher likelihood of developing obesity as adults. The amount and quality of food that the mother consumes during gestation influences birth weight, and therefore susceptibility of progeny to disease in later life. Studies in experimental animals support these observations, and find that obesity occurs as a result of maternal nutrient-restriction during gestation, followed by rapid compensatory growth associated with ad libitum food consumption. Therefore, obesity associated with maternal nutritional restriction has a developmental origin. Based on this phenomenon, one might predict that gestational exposure to a westernized diet would protect against future obesity in offspring. However, evidence from experimental models indicates that, like maternal dietary restriction, maternal consumption of a westernized diet during gestation and lactation interacts with an adult obesogenic diet to induce further obesity. Mechanistically, restriction of nutrients or consumption of a high fat diet during gestation may promote obesity in progeny by altering hypothalamic neuropeptide production and thereby increasing hyperphagia in offspring. In addition to changes in food intake these animals may also direct energy from muscle toward storage in adipose tissue. Surprisingly, generational inheritance studies in rodents have further indicated that effects on body length, body weight, and glucose tolerance appear to be propagated to subsequent generations. Together, the findings discussed herein highlight the concept that maternal nutrition contributes to a legacy of obesity. Thus, ensuring adequate supplies of a complete and balanced diet during and after pregnancy should be a priority for public health worldwide. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

Keywords: Maternal health; Nutrition; Obesity.

Figure 1

Epidemiological studies have described a J- or U-shaped relationship between birth weight (a marker of fetal nutritional exposure) and the propensity to develop obesity in adulthood.

Figure 2

Fetal exposure to maternal global- or protein-restriction during gestation decreases amino acid transfer through the placenta leading to intrauterine growth restriction (IUGR). IUGR leads to decreased β-cell mass, and altered timing (IUGR indicated in red, Control in black) or amplitude of the developmental leptin surge. The decrease surge contributes to leptin resistance, increased orexigenic neuropeptide production and hyperphagia. Compensatory growth may favor deposition of adipose tissue with energy redistributed from insulin-resistant skeletal muscle towards insulin-sensitive adipocytes.

Figure 3

Exposure to maternal obesogenic diet through gestation and lactation increases placental inflammation resulting in modified amino acid transport and fetal growth including decreased β-cell mass. Following birth, maternal high fat diet consumption through lactation increases milk volume and lipid concentration, increasing circulating blood lipids, and causing neonatal neuroepithelial cells to undergo mitosis, differentiation and translocation into the hypothalamus where they elevate levels of orexigenic neuropeptides. When combined with accompanying leptin resistance, this increase in orexigenic neuropeptide production stimulates offspring hyperphagia and obesity.