Abstract
Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to and throughout pregnancy and lactation. We now report that offspring of obese (OffOb) rats display an amplified and prolonged neonatal leptin surge, which is accompanied by elevated leptin mRNA expression in their abdominal white adipose tissue. At postnatal Day 30, before the onset of hyperphagia in these animals, serum leptin is normal, but leptin-induced appetite suppression and phosphorylation of STAT3 in the arcuate nucleus (ARC) are attenuated; the level of AgRP-immunoreactivity in the hypothalamic paraventricular nucleus (PVH), which derives from neurones in the ARC and is developmentally dependent on leptin, is also diminished. We hypothesise that prolonged release of abnormally high levels of leptin by neonatal OffOb rats leads to leptin resistance and permanently affects hypothalamic functions involving the ARC and PVH. Such effects may underlie the developmental programming of hyperphagia and obesity in these rats.
Highlights
The developmental overnutrition hypothesis suggests that maternal obesity and/or gestational diabetes in humans may predispose offspring to altered energy balance and increased adiposity in adulthood [1,2,3,4]
We have recently reported that offspring of mice or rats in which obesity had been induced by prolonged consumption of an obesogenic diet display hyperphagia, increased fat mass and hyperleptinaemia in adulthood [8,9]
Development of Maternal Obesity Female Sprague Dawley rats consuming the highly palatable fat- and sugar-rich diet became significantly heavier than control animals after 10 days (Fig. 1A)
Summary
The developmental overnutrition hypothesis suggests that maternal obesity and/or gestational diabetes in humans may predispose offspring to altered energy balance and increased adiposity in adulthood [1,2,3,4]. This hypothesis has gained strength with recent reports of an association between excessive weight gain in pregnancy and the BMI of the adolescent child and of a greater influence of maternal BMI than paternal BMI on offspring adiposity [5,6,7]. We have characterised the neonatal profiles of serum leptin and adipose leptin mRNA and the composition of ingested milk in the offspring of obese dams (OffOb rats) To our knowledge, this is the first study to investigate the effects of maternal obesity on the neonatal leptin surge. This study thereby investigates the processes underlying the non-genetic transmission of an obesogenic trait from mother to offspring
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