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Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring.

Kirk SL, Samuelsson AM, Argenton M, Dhonye H, Kalamatianos T, Poston L, Taylor PD, Coen CW - PLoS ONE (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Reproduction and Endocrinology, King's College London, London, UK.

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.

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Related in: MedlinePlus

Signalling responses to leptin in juvenile and adult offspring of control and obese dams.Representative images (A) and quantitative analysis (B and C) of leptin-induced pSTAT3-immunoreactive (ir) cells (per mm2) in the arcuate nucleus (ARC) and ventromedial hypothalamic nucleus (VMH). Leptin (10 mg/kg, i.p.) was administered 45 min prior to administration of anaesthetic and perfusion fixation of the brain. OffCon = offspring of control dams; OffOb = offspring of obese dams; dl = dorsolateral; vl = ventrolateral. * p<0.05 versus offspring of control dams (n = 4–8).
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pone-0005870-g006: Signalling responses to leptin in juvenile and adult offspring of control and obese dams.Representative images (A) and quantitative analysis (B and C) of leptin-induced pSTAT3-immunoreactive (ir) cells (per mm2) in the arcuate nucleus (ARC) and ventromedial hypothalamic nucleus (VMH). Leptin (10 mg/kg, i.p.) was administered 45 min prior to administration of anaesthetic and perfusion fixation of the brain. OffCon = offspring of control dams; OffOb = offspring of obese dams; dl = dorsolateral; vl = ventrolateral. * p<0.05 versus offspring of control dams (n = 4–8).

Mentions: The processes underlying the behavioural evidence for leptin resistance were investigated by determining the number of cells immunoreactive for pSTAT3, which is induced following activation of leptin receptors [24], in the ARC and ventromedial hypothalamic nucleus (VMH) in response to exogenous leptin (10 mg/kg, i.p.). In the ARC, at approximately 3.30 mm caudal to bregma, OffOb rats displayed fewer pSTAT3-immunoreactive neurons than OffCon rats (Fig. 6 A,B). No evidence of impaired leptin-signalling was found in the VMH (Fig. 6G).


Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring.

Kirk SL, Samuelsson AM, Argenton M, Dhonye H, Kalamatianos T, Poston L, Taylor PD, Coen CW - PLoS ONE (2009)

Signalling responses to leptin in juvenile and adult offspring of control and obese dams.Representative images (A) and quantitative analysis (B and C) of leptin-induced pSTAT3-immunoreactive (ir) cells (per mm2) in the arcuate nucleus (ARC) and ventromedial hypothalamic nucleus (VMH). Leptin (10 mg/kg, i.p.) was administered 45 min prior to administration of anaesthetic and perfusion fixation of the brain. OffCon = offspring of control dams; OffOb = offspring of obese dams; dl = dorsolateral; vl = ventrolateral. * p<0.05 versus offspring of control dams (n = 4–8).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2690656&req=5

pone-0005870-g006: Signalling responses to leptin in juvenile and adult offspring of control and obese dams.Representative images (A) and quantitative analysis (B and C) of leptin-induced pSTAT3-immunoreactive (ir) cells (per mm2) in the arcuate nucleus (ARC) and ventromedial hypothalamic nucleus (VMH). Leptin (10 mg/kg, i.p.) was administered 45 min prior to administration of anaesthetic and perfusion fixation of the brain. OffCon = offspring of control dams; OffOb = offspring of obese dams; dl = dorsolateral; vl = ventrolateral. * p<0.05 versus offspring of control dams (n = 4–8).
Mentions: The processes underlying the behavioural evidence for leptin resistance were investigated by determining the number of cells immunoreactive for pSTAT3, which is induced following activation of leptin receptors [24], in the ARC and ventromedial hypothalamic nucleus (VMH) in response to exogenous leptin (10 mg/kg, i.p.). In the ARC, at approximately 3.30 mm caudal to bregma, OffOb rats displayed fewer pSTAT3-immunoreactive neurons than OffCon rats (Fig. 6 A,B). No evidence of impaired leptin-signalling was found in the VMH (Fig. 6G).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Reproduction and Endocrinology, King's College London, London, UK.

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.

Show MeSH
Related in: MedlinePlus