Role of Leptin in Orexigenic Neuropeptide Expression During Lactation in Rats

Abstract

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.

The differences in feeding-inhibitory responses to peripheral and central leptin between non-lactating and lactating rats

“…We confirmed that plasma leptin levels were consistently lower in lactating rats than in non-lactating rats as has been reported (Denis et al 2003a, Asakuma et al 2004 Crowley et al 2004). Low circulating leptin levels would contribute to the hyperphagia of lactating rats.…”

“…Consequently, food consumption increases several fold during lactation. Compared to non-lactating rats, lactating rats display significantly lower serum concentrations of an anorexigenic peptide leptin (Vernon et al 2002, Crowley et al 2004.…”

Plasticity in gastrointestinal morphology and enzyme activity in lactating striped hamsters (Cricetulus barabensis)

“…In the present study, AgRP mRNA expression was significantly up-regulated in striped hamsters raising larger litter sizes, whereas NPY, POMC and CART mRNA expression did not differ between the hamsters raising different litter sizes. This is partly consistent with the observation that in lactating rats, both NPY and AgRP are greatly elevated (Chen et al, 2004;Crowley et al, 2004;Li et al, 1999;Malabu et al, 1994;Pickavance et al, 1999;Smith, 1993;Suzuki et al, 2014), but the increase in AgRP mRNA expression during lactation is especially marked (Suzuki et al, 2014). POMC and/or CART mRNA expression significantly decreased during lactation in comparison with the non-lactation period (Brogan et al, 2000;Smith, 1993;Sorensen et al, 2002;Suzuki et al, 2014).…”

“…The neuroendocrine basis of hyperphagia in lactation is suggested to be triggered by hypothalamic neuropeptides, such as the orexigenic neuropeptides NPY and AgRP, and the anorexigenic neuropeptides POMC and CART (Brogan et al, 2000;Chen et al, 2004;Crowley et al, 2004;Malabu et al, 1994;Li et al, 1999;Pickavance et al, 1999;Smith, 1993;Sorensen et al, 2002;Suzuki et al, 2014). In the present study, AgRP mRNA expression was significantly up-regulated in striped hamsters raising larger litter sizes, whereas NPY, POMC and CART mRNA expression did not differ between the hamsters raising different litter sizes.…”

Gestational weight gain by reduced brain melanocortin activity affects offspring energy balance in rats

“…This could be relevant as plasma leptin levels are normally suppressed during lactation in rats. [39][40][41][42] Together with an increased expression of some of the short forms of the leptin receptor (Ob-Re and Ob-Rf) in the hypothalamus 43 and an increased leptin-binding activity in plasma, 41 this could have accounted for the suppression of MC signalling during lactation as well. An additional explanation may be that AgRP (as opposed to the 'passive' receptor blocker SHU9119) acts as an inverse agonist on MC4 receptors, 44 which could gate other orexigenic systems postsynaptically to maximize ingestive behaviour.…”