Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity

Abstract

A series of epidemiological, clinical and experimental studies have shown that there are associations between the fetal and neonatal nutritional environment and the amount and distribution of adipose tissue in adult life. This review considers the evidence for these relationships and discusses the potential impact of the prenatal nutritional experience on the development of the endocrine and neuroendocrine systems that regulate energy balance, with a particular emphasis on the role of the adipocyte-derived hormone, leptin. In the rodent, leptin derived from the mother may exert an important influence on the development of the appetite regulatory neural network and on the subsequent regulation of leptin synthesis and the risk for obesity in the offspring. In species such as the human and sheep, there is also recent evidence that the synthesis and secretion of adipocyte-derived hormones, such as leptin, are regulated in fetal life. Furthermore, the hypothalamic neuropeptides that regulate energy intake and expenditure in adult life are also present within the fetal brain and may be regulated by the prevailing level of maternal and hence fetal nutrient and hormonal signals, including leptin. This work is important in determining those initiating mechanisms within the 'fat -brain' axis in early life that precede the development of adult obesity.

Maternal Dietary Patterns during Pregnancy Are Associated with Child Growth in the First 3 Years of Life

“…Pregnant rats fed a junk-food diet during gestation and lactation produced offspring with higher adiposity (29,30). One potential biological mechanism that may explain the associations found in the present study is leptin action, synthesis, and secretion (31). An intrauterine environment exposed to poor maternal nutrition could cause low fetal glucose, insulin, and leptin concentrations, leading to reduced birth weight and rapid postnatal growth because of increased appetite in early postnatal life (31).…”

“…One potential biological mechanism that may explain the associations found in the present study is leptin action, synthesis, and secretion (31). An intrauterine environment exposed to poor maternal nutrition could cause low fetal glucose, insulin, and leptin concentrations, leading to reduced birth weight and rapid postnatal growth because of increased appetite in early postnatal life (31). Unfortunately, testing this hypothesis directly is impractical because of the difficulty of measuring fetal glucose, insulin, and leptin concentrations directly.…”

Role of leptin in female reproduction

“…It is well known that serum leptin levels are higher in pregnant as compared to non-pregnant women [115][116][117]. Moreover, serum leptinemia correlates with maternal body weight [118]. However, this elevation does not appear to be mediated by increased body weight and adiposity, since circulating leptin concentrations increase dramatically well before the occurrence of increased body weight [116].…”

Early postnatal leptin blockage leads to a long-term leptin resistance and susceptibility to diet-induced obesity in rats

“…Several recent discoveries indicate that leptin may play a critical role in the establishment of this programming. 6,7 Leptin is a 16-kDa cytokine synthesized and secreted essentially by adipocytes and also by several ectopic sources such as placenta, 8 mammary gland 9,10 and stomach 11,12 and is involved in an impressive list of biological effects. 13 Leptin, through its long isoform receptor, plays a pivotal role on food intake regulation and exerts its actions at the central level in the hypothalamus within a neuronal network integrating a wide range of nervous, nutritional and hormonal signals.…”