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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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Post-weaning characteristics of offspring of control and obese dams.Body weight for males (A) and females (B) and calorific intake for males (C) and females (D) were recorded post-weaning for offspring of control (open symbols) or obese (closed symbols) dams. Offspring body and tissue weights were recorded at postnatal Day 90 (E). OffCon = offspring of control dams; OffOb = offspring of obese dams; WAT = white adipose tissue; BAT = brown adipose tissue; s.c. = subcutaneous. * p<0.05 and ** p<0.01 versus offspring of control dams (n = 8–11).
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pone-0005870-g002: Post-weaning characteristics of offspring of control and obese dams.Body weight for males (A) and females (B) and calorific intake for males (C) and females (D) were recorded post-weaning for offspring of control (open symbols) or obese (closed symbols) dams. Offspring body and tissue weights were recorded at postnatal Day 90 (E). OffCon = offspring of control dams; OffOb = offspring of obese dams; WAT = white adipose tissue; BAT = brown adipose tissue; s.c. = subcutaneous. * p<0.05 and ** p<0.01 versus offspring of control dams (n = 8–11).

Mentions: Male and female OffOb rats were heavier at weaning than offspring of control dams (OffCon rats; Fig. 2A,B); however, by 30 days of age, after weaning onto standard chow, body weight was similar between the two groups (body weight [g]: OffCon males: 100.9±2.5 versus OffOb males 100.1±4.3 males; OffCon females 96.4±1.7 versus OffOb females 94.8±3.1). OffOb rats developed hyperphagia from 5–6 weeks of age, showing a significant increase in calorific intake and body weight, which persisted into adulthood (Fig. 2A–D). At 90 days of age, OffOb rats weighed more than OffCon rats (body weight [g]: OffCon males 390.0±14.2 versus OffOb males 473.5±9.8 males p<0.01; OffCon females 265.6±8.5 versus OffOb females 307.3±13.2 p<0.05) and had markedly greater fat mass than OffCon rats in the inguinal, dorsal (interscapular) subcutaneous, mesenteric (males only) and perirenal (females only) fat pads (Fig. 2E). Liver weight was significantly greater in OffOb males and females; hearts were heavier only in OffOb males (Fig. 2E). Weights of brown adipose tissue and soleus and vastus lateralis muscles were similar in OffOb and OffCon animals (Fig. 2E).


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)

Post-weaning characteristics of offspring of control and obese dams.Body weight for males (A) and females (B) and calorific intake for males (C) and females (D) were recorded post-weaning for offspring of control (open symbols) or obese (closed symbols) dams. Offspring body and tissue weights were recorded at postnatal Day 90 (E). OffCon = offspring of control dams; OffOb = offspring of obese dams; WAT = white adipose tissue; BAT = brown adipose tissue; s.c. = subcutaneous. * p<0.05 and ** p<0.01 versus offspring of control dams (n = 8–11).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2690656&req=5

pone-0005870-g002: Post-weaning characteristics of offspring of control and obese dams.Body weight for males (A) and females (B) and calorific intake for males (C) and females (D) were recorded post-weaning for offspring of control (open symbols) or obese (closed symbols) dams. Offspring body and tissue weights were recorded at postnatal Day 90 (E). OffCon = offspring of control dams; OffOb = offspring of obese dams; WAT = white adipose tissue; BAT = brown adipose tissue; s.c. = subcutaneous. * p<0.05 and ** p<0.01 versus offspring of control dams (n = 8–11).
Mentions: Male and female OffOb rats were heavier at weaning than offspring of control dams (OffCon rats; Fig. 2A,B); however, by 30 days of age, after weaning onto standard chow, body weight was similar between the two groups (body weight [g]: OffCon males: 100.9±2.5 versus OffOb males 100.1±4.3 males; OffCon females 96.4±1.7 versus OffOb females 94.8±3.1). OffOb rats developed hyperphagia from 5–6 weeks of age, showing a significant increase in calorific intake and body weight, which persisted into adulthood (Fig. 2A–D). At 90 days of age, OffOb rats weighed more than OffCon rats (body weight [g]: OffCon males 390.0±14.2 versus OffOb males 473.5±9.8 males p<0.01; OffCon females 265.6±8.5 versus OffOb females 307.3±13.2 p<0.05) and had markedly greater fat mass than OffCon rats in the inguinal, dorsal (interscapular) subcutaneous, mesenteric (males only) and perirenal (females only) fat pads (Fig. 2E). Liver weight was significantly greater in OffOb males and females; hearts were heavier only in OffOb males (Fig. 2E). Weights of brown adipose tissue and soleus and vastus lateralis muscles were similar in OffOb and OffCon animals (Fig. 2E).

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