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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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Behavioural responses to leptin in juvenile and adult offspring of control and obese dams.Food intake for males (A) and females (B) and change in body weight for males (C) and females (D) recorded over 24 hours following administration of leptin (10 mg/kg, i.p.) in 30 day-old offspring of control or obese dams. Food intake for males (E) and females (F) and change in body weight for males (G) and females (H) in 90 day-old offspring of control or obese dams. OffCon = offspring of control dams; OffOb = offspring of obese dams; * p<0.05 and ** p<0.01 ***p<0.001, versus offspring of control dams (n = 6).
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pone-0005870-g005: Behavioural responses to leptin in juvenile and adult offspring of control and obese dams.Food intake for males (A) and females (B) and change in body weight for males (C) and females (D) recorded over 24 hours following administration of leptin (10 mg/kg, i.p.) in 30 day-old offspring of control or obese dams. Food intake for males (E) and females (F) and change in body weight for males (G) and females (H) in 90 day-old offspring of control or obese dams. OffCon = offspring of control dams; OffOb = offspring of obese dams; * p<0.05 and ** p<0.01 ***p<0.001, versus offspring of control dams (n = 6).

Mentions: The possibility that OffOb rats are leptin resistant was investigated at Day 30, when endogenous circulating levels of leptin showed no significant differences between OffOb and OffCon rats (leptin [ng/ml]: OffCon males: 3.5±0.5 versus OffOb males 2.8±0.4 males; OffCon females 3.6±0.3 versus OffOb females 3.0±0.7). Leptin (10 mg/kg) administered intraperitoneally failed to reduce food intake and body weight over a 24-hour period in male and female OffOb rats compared with OffCon rats (Fig. 5A–D). This resistance to the appetite- and weight-reducing actions of leptin was also apparent at Day 90 (Fig. 5E–H), when the serum leptin concentration was significantly higher in OffOb rats (leptin [ng/ml]: OffOb males 21.74±1.84 versus OffCon males 15.68±0.73, P<0.01; OffOb females 10.71±1.23 versus OffCon females 7.92±0.90, P<0.05).


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)

Behavioural responses to leptin in juvenile and adult offspring of control and obese dams.Food intake for males (A) and females (B) and change in body weight for males (C) and females (D) recorded over 24 hours following administration of leptin (10 mg/kg, i.p.) in 30 day-old offspring of control or obese dams. Food intake for males (E) and females (F) and change in body weight for males (G) and females (H) in 90 day-old offspring of control or obese dams. OffCon = offspring of control dams; OffOb = offspring of obese dams; * p<0.05 and ** p<0.01 ***p<0.001, versus offspring of control dams (n = 6).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0005870-g005: Behavioural responses to leptin in juvenile and adult offspring of control and obese dams.Food intake for males (A) and females (B) and change in body weight for males (C) and females (D) recorded over 24 hours following administration of leptin (10 mg/kg, i.p.) in 30 day-old offspring of control or obese dams. Food intake for males (E) and females (F) and change in body weight for males (G) and females (H) in 90 day-old offspring of control or obese dams. OffCon = offspring of control dams; OffOb = offspring of obese dams; * p<0.05 and ** p<0.01 ***p<0.001, versus offspring of control dams (n = 6).
Mentions: The possibility that OffOb rats are leptin resistant was investigated at Day 30, when endogenous circulating levels of leptin showed no significant differences between OffOb and OffCon rats (leptin [ng/ml]: OffCon males: 3.5±0.5 versus OffOb males 2.8±0.4 males; OffCon females 3.6±0.3 versus OffOb females 3.0±0.7). Leptin (10 mg/kg) administered intraperitoneally failed to reduce food intake and body weight over a 24-hour period in male and female OffOb rats compared with OffCon rats (Fig. 5A–D). This resistance to the appetite- and weight-reducing actions of leptin was also apparent at Day 90 (Fig. 5E–H), when the serum leptin concentration was significantly higher in OffOb rats (leptin [ng/ml]: OffOb males 21.74±1.84 versus OffCon males 15.68±0.73, P<0.01; OffOb females 10.71±1.23 versus OffCon females 7.92±0.90, P<0.05).

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