Evidence for involvement of neuropeptide Y and melanocortin systems in the hyperphagia of lactation in rats

Crowley, William R.; Ramoz, Gina; Hurst, Brianne

doi:10.1016/s0091-3057(02)01006-7

Cited by 15 publications

(14 citation statements)

References 29 publications

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“…It seems likely that, under these 'maximized' intake conditions, MC4 receptor signalling is already completely abolished , leaving nothing left to block with SHU9119. In line with this observation is the report by Crowley et al 37,38 that mRNA expression of AgRP in the ARC is strongly upregulated, which is probably mediated by suckling. AgRP may lead to maximal suppression of brain MC receptor signalling, rendering additional pharmacological inhibition of brain MC receptors ineffective.…”

Section: Discussionsupporting

confidence: 73%

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

Heinsbroek

Dijk

2008

Int J Obes

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Introduction: Excessive gestational body weight gain of mothers may predispose offspring towards obesity and metabolic derangements. It is difficult to discern the effects of maternal obesogenic factorsFsuch as diet and/or thrifty genetic predispositionFfrom gestational weight gain per se. Methods: For this reason, genetically normal Wistar rats that were fed regular chow were rendered hypothalamically obese by chronic third-cerebral ventricular (i3vt) infusion during pregnancy and lactation with the melanocortin-3,4 receptor blocker SHU9119. This procedure caused significant increases in body weight gain during pregnancy and lactation compared with controls, and the effects thereof on offspring energy balance and fuel homeostasis were investigated. Results: At birth, litter weight and size, but not individual pup weight, of SHU9119-treated mothers were significantly smaller than controls. In litters culled to eight, pup weight gain during lactation was only transiently increased by treatment. After weaning, however, male offspring of SHU9119-treated mothers became increasingly heavier over time relative to controls until killing at 9 months. This effect was only transient in females. Increased body weights of males were not associated with disturbances in glucose homeostasis, but with increased energy expenditure instead. Multiple regression analysis revealed that gestational body weight gain, irrespective of the group, contributed positively to increased visceral fat deposition and carbohydrate oxidation in the male offspring. In contrast, the pre-pregnancy body weight of mothers contributed positively to male offspring daily energy expenditure, subcutaneous fat and eviscerated carcass as well as structural organ weights. In female offspring, gestational body weight gain, but not pre-gestational body weight, contributed both to aspects of weight gain as well as to the shift of fat oxidation toward carbohydrate oxidation. Conclusion: Gestational weight gain induced by low brain melanocortin receptor activity can lead to increased body weight gain in the offspring (particularly in males) independent of obesogenic dietary and/or thrifty genetic predisposition.

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Section: Discussionsupporting

confidence: 73%

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

Heinsbroek

Dijk

2008

Int J Obes

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“…When a large energy demand is present, such as milk production, NPY expression in the DMH will provide an additional signal to the PVH to further increase food intake. This view is supported by the findings from Crowley et al (2003) showing that heightened NPY expression and lowered MC4R signaling is the main driving force for the hyperphagia in lactation. This study showed that central injections of a NPY antagonist and ␣-MSH (at a dose much higher than normally used to suppress feeding in normal female rats) reduced food intake of lactating rats to ϳ40% of normal.…”

Section: Discussionmentioning

confidence: 63%

Melanocortin 4 Receptor-Mediated Hyperphagia and Activation of Neuropeptide Y Expression in the Dorsomedial Hypothalamus during Lactation

Chen¹,

Williams²,

Grove³

et al. 2004

J. Neurosci.

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In several hyperphagic models, including lactation, in which hypothalamic melanocortin signaling is reduced, a novel expression of NPY mRNA in the dorsomedial hypothalamus (DMH) has been observed, suggesting that melanocortin signaling and the induced NPY in the DMH may constitute unique neurocircuitry in mediating energy balance. Using lactating rats as a model, the present study first showed that in the DMH abundant ␣-MSH and agouti-related protein fibers are in close apposition to NPY-positive cells. However, no NPY and MC4R (a melanocortin receptor) double-labeled neurons were observed. These data suggested that melanocortin input may synapse on presynaptic terminals that then synapse on DMH NPY cells. To study the function of DMH MC4Rs in energy balance, an MC3/4R-selective agonist, melanotan II (MTII), was injected bilaterally into the DMH. MTII injection significantly suppressed feeding induced by 24 hr fasting or suckling-induced hyperphagia. Furthermore, MTII treatment greatly attenuated suckling-induced NPY expression in the DMH. MTII treatment also stimulated uncoupling protein 1 activity in the brown adipose tissue of suckling female rats, indicative of increased sympathetic outflow. In summary, the present study demonstrated that the melanocortin system in the DMH not only plays an important role in inducing NPY expression in the DMH of lactating rats but also in regulating energy homeostasis, at least in part, by modulating appetite and energy expenditure.

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“…The POMC gene products are downregulated during lactation [12,17,26,28], but see [4]. A decrease in melanocyte-stimulating hormone (a product of POMC that inhibits feeding) ( Table 2 and Fig.2) along with the elevations in NPY seen during lactation here and in other studies [8,38], have been proposed to explain the hyperphagia that occurs during lactation [9].…”

Section: Gene Expression Changes During Lactation Consistent With Prementioning

confidence: 57%

Gene array profiling of large hypothalamic CNS regions in lactating and randomly cycling virgin mice

Gammie

Hasen

Awad³

et al. 2005

Molecular Brain Research

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A dramatic example of neuronal and physiological plasticity in adult mammals occurs during the transition from a non-maternal to a maternal, lactating state. In this study we compared gene expression within a large continuous region of the CNS involved in maternal behaviors (hypothalamus, preoptic regions, and nucleus accumbens) between lactating (L) (postpartum Day 7) and randomly cycling virgin (V) outbred mice. Using high density oligonucleotide arrays representing 11,904 genes, two statistical algorithms were used to identify significant differences in gene expression: robust multi array (p < 0.001) (n = 92 genes) and significance analysis of microarrays using a 10% false discover rate (n = 114 genes). 27 common genes were identified as significant using both techniques. A subset of genes (n = 5) were selected and examined by real-time PCR. Our findings were consistent with previous published work. For example, neuropeptide Y (NPY) and proenkephalin were elevated in L mice, whereas POMC was decreased. Increased levels of NPY Y2 receptor and polo-like kinase and decreased levels of endothelin receptor type b in L mice are examples of novel gene expression changes not previously identified. Expression differences occurred in broad classes. Together, our findings provide possible new material on gene expression changes that may support maternal behaviors. The advantages and drawbacks of sampling large CNS regions using arrays are discussed.

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Evidence for involvement of neuropeptide Y and melanocortin systems in the hyperphagia of lactation in rats

Cited by 15 publications

References 29 publications

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

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

Melanocortin 4 Receptor-Mediated Hyperphagia and Activation of Neuropeptide Y Expression in the Dorsomedial Hypothalamus during Lactation

Gene array profiling of large hypothalamic CNS regions in lactating and randomly cycling virgin mice

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