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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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Constituents of milk from control and obese dams by analysis of pups' stomach contents.The concentration of leptin (A), cholesterol (B), free fatty acids (FFA) (C), triglycerides (D) and glucose (E) was assayed in stomach contents (as a proxy measure of the dams' milk content) from offspring of control dams (open bars; n = 4–8) and obese dams (closed bars; n = 4–8) throughout suckling. * p<0.05 and ** p<0.01 versus offspring of control dams at the same period. For longitudinal comparisons, a significant difference (p<0.05) from the preceding period is indicated by # for offspring of control dams and by † for offspring of obese dams.
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pone-0005870-g004: Constituents of milk from control and obese dams by analysis of pups' stomach contents.The concentration of leptin (A), cholesterol (B), free fatty acids (FFA) (C), triglycerides (D) and glucose (E) was assayed in stomach contents (as a proxy measure of the dams' milk content) from offspring of control dams (open bars; n = 4–8) and obese dams (closed bars; n = 4–8) throughout suckling. * p<0.05 and ** p<0.01 versus offspring of control dams at the same period. For longitudinal comparisons, a significant difference (p<0.05) from the preceding period is indicated by # for offspring of control dams and by † for offspring of obese dams.

Mentions: Given the putative role of the rodent neonatal leptin surge in persistent effects on offspring energy balance, we investigated leptin profiles in pup serum and stomach contents (as a proxy measure of the dam's milk content) over the suckling period. The serum leptin profile, which typically shows a surge during the neonatal period [21]–[23] was greatly amplified and prolonged in OffOb rats (Fig. 3A). In OffCon rats the leptin surge showed two peaks: an initial peak at postnatal Day 8 and a second smaller peak at Day 14. In contrast, the leptin surge in OffOb rats remained elevated throughout the latter period of lactation, being significantly higher than in OffCon rats on postnatal days 7, 9, 11, 13, 14, 15 and 18 (Fig. 3A). The leptin mRNA profile in pup abdominal white adipose tissue sampled from birth to weaning showed significantly greater expression in OffOb rats during the extended period of their leptin surge (Fig. 3B). This suggests that the pup's adipocytes are the principal source of the amplified and prolonged serum leptin surge. The possibility that the leptin concentration in the dam's milk, as estimated from the stomach contents of the pups, contributed to the serum leptin profile was investigated; however, the mismatch between the ingested and serum leptin profiles in OffOB and OffCon rats failed to support this hypothesis (Fig. 4A). Furthermore, the leptin concentration in the stomach contents was at least two orders of magnitude lower than in the pup's serum. Nevertheless, the profiles of ingested cholesterol, free fatty acids, triglycerides and glucose in OffOb rats showed a marked rise on postnatal days 9–11 (Fig. 4B–E); this coincided with the onset of sustained elevated serum leptin (Fig. 3A). Analysis of the fatty acid profiles in the milk during the leptin surge (Days 9–18) showed an increase in the ratio of arachidonic acid (n-6) to eicosapentaenoic and docosahexaenoic acids (n-3): n-6∶n-3 ratio [mean±SD]: OffCon 1.71±0.54 vs. OffOb 3.85±1.59, P<0.01.


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)

Constituents of milk from control and obese dams by analysis of pups' stomach contents.The concentration of leptin (A), cholesterol (B), free fatty acids (FFA) (C), triglycerides (D) and glucose (E) was assayed in stomach contents (as a proxy measure of the dams' milk content) from offspring of control dams (open bars; n = 4–8) and obese dams (closed bars; n = 4–8) throughout suckling. * p<0.05 and ** p<0.01 versus offspring of control dams at the same period. For longitudinal comparisons, a significant difference (p<0.05) from the preceding period is indicated by # for offspring of control dams and by † for offspring of obese dams.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0005870-g004: Constituents of milk from control and obese dams by analysis of pups' stomach contents.The concentration of leptin (A), cholesterol (B), free fatty acids (FFA) (C), triglycerides (D) and glucose (E) was assayed in stomach contents (as a proxy measure of the dams' milk content) from offspring of control dams (open bars; n = 4–8) and obese dams (closed bars; n = 4–8) throughout suckling. * p<0.05 and ** p<0.01 versus offspring of control dams at the same period. For longitudinal comparisons, a significant difference (p<0.05) from the preceding period is indicated by # for offspring of control dams and by † for offspring of obese dams.
Mentions: Given the putative role of the rodent neonatal leptin surge in persistent effects on offspring energy balance, we investigated leptin profiles in pup serum and stomach contents (as a proxy measure of the dam's milk content) over the suckling period. The serum leptin profile, which typically shows a surge during the neonatal period [21]–[23] was greatly amplified and prolonged in OffOb rats (Fig. 3A). In OffCon rats the leptin surge showed two peaks: an initial peak at postnatal Day 8 and a second smaller peak at Day 14. In contrast, the leptin surge in OffOb rats remained elevated throughout the latter period of lactation, being significantly higher than in OffCon rats on postnatal days 7, 9, 11, 13, 14, 15 and 18 (Fig. 3A). The leptin mRNA profile in pup abdominal white adipose tissue sampled from birth to weaning showed significantly greater expression in OffOb rats during the extended period of their leptin surge (Fig. 3B). This suggests that the pup's adipocytes are the principal source of the amplified and prolonged serum leptin surge. The possibility that the leptin concentration in the dam's milk, as estimated from the stomach contents of the pups, contributed to the serum leptin profile was investigated; however, the mismatch between the ingested and serum leptin profiles in OffOB and OffCon rats failed to support this hypothesis (Fig. 4A). Furthermore, the leptin concentration in the stomach contents was at least two orders of magnitude lower than in the pup's serum. Nevertheless, the profiles of ingested cholesterol, free fatty acids, triglycerides and glucose in OffOb rats showed a marked rise on postnatal days 9–11 (Fig. 4B–E); this coincided with the onset of sustained elevated serum leptin (Fig. 3A). Analysis of the fatty acid profiles in the milk during the leptin surge (Days 9–18) showed an increase in the ratio of arachidonic acid (n-6) to eicosapentaenoic and docosahexaenoic acids (n-3): n-6∶n-3 ratio [mean±SD]: OffCon 1.71±0.54 vs. OffOb 3.85±1.59, P<0.01.

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