Role of Leptin in Orexigenic Neuropeptide Expression During Lactation in Rats

Jun 25, 2004Journal of neuroendocrinology

Leptin's role in hunger-related brain signals during breastfeeding in rats

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Abstract

Lactating female rats displayed significantly lower serum concentrations of insulin and leptin, along with increased neuropeptide Y (NPY) and agouti-related peptide (AgRP) expression.

During lactation, expression of NPY and AgRP is up-regulated in the arcuate nucleus of the hypothalamus.
Lactating rats exhibited significantly increased NPY peptide levels in the paraventricular nucleus and median eminence compared to non-lactating rats.
Infusion of leptin in lactating females led to an increase in serum leptin and a significant decrease in NPY concentrations.
Insulin infusion also restored serum concentrations and reduced both NPY and AgRP mRNA levels in lactating rats.
No significant differences were observed in pro-opiomelanocortin mRNA levels between non-lactating and lactating females.

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The expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP), both of which are important neuropeptides involved in regulation of energy balance and hormone secretion, is up-regulated in the arcuate nucleus during lactation in rodents. The present study tested whether reductions in circulating insulin and/or leptin that occur in lactation provide the critical signals to these systems. Lactating female rats received 3-day infusions of either bovine insulin or recombinant rat leptin via Alzet Osmotic minipumps implanted subcutaneously in regimens designed to restore serum concentrations of these hormones to the higher non-lactating level. Compared to non-lactating rats in diestrus, lactating rats displayed significantly lower serum concentrations of insulin and leptin, and significantly increased NPY peptide concentrations in the paraventricular nucleus (PVN) and median eminence, and AgRP mRNA in the arcuate nucleus. Infusion of leptin in lactating females significantly increased serum concentrations of leptin and significantly reduced NPY concentrations in the PVN and median eminence, and decreased NPY and AgRP mRNAs in the arcuate nucleus. The same effects were produced by infusion of insulin in lactating rats, which restored both insulin and leptin concentrations in serum. The levels of pro-opiomelanocortin mRNA in the arcuate nucleus were not different in non-lactating and lactating females, and were not altered by leptin or insulin treatment. These findings support the hypothesis that the reduction in circulating leptin during lactation contributes to increased expression of NPY and AgRP in hypothalamic systems involved in the behavioural and neuroendocrine adaptations to lactation.

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Role of Leptin in Orexigenic Neuropeptide Expression During Lactation in Rats

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