Neonatal ghrelin programs development of hypothalamic feeding circuits

Steculorum, Sophie M.; Colldén, Gustav; Coupé, Bérengère; Croizier, Sophie; Lockie, Sarah H.; Andrews, Zane B.; Jarosch, Florian; Klussmann, Sven; Bouret, Sébastien G.

doi:10.1172/jci73688

Cited by 135 publications

(117 citation statements)

References 56 publications

(82 reference statements)

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“…These effects can lead to lifelong deficits in satiety and metabolic signalling and 164 pronounced obesity (Bouret et al, 2004b;Steculorum et al, 2015). Ob/ob mice that do not 165 produce leptin are obese compared with controls of the same age and have a substantially 166 reduced density of fibres projecting from the ARC to the PVN and other regions of the 167 hypothalamus (Bouret et al, 2004b).…”

Section: Perinatal Programming Of Metabolic Circuitry 161mentioning

confidence: 99%

“…These synapses 134 continue to mature functionally from birth through to adulthood with, for instance, PVN 135 neurons being relatively unresponsive to melanocortin at one week of age but highly concentrations increasing between P10 and P14 and at this point acting to curtail leptin-154 stimulated neurite growth (Steculorum et al, 2015). Insulin is a third hormone important in 155 the development of this circuitry.…”

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confidence: 99%

“…However, its influence on ghrelin sensitivity is only transient, with normal 232 responses to exogenous ghrelin seen in neonatally overfed adults (Sominsky et al, 2017a). It 233 is noteworthy that even in the mouse, body weight and density of ARC axons are normal by 234 P35 in ghrelin knockouts, indicating compensatory factors likely play a role in the case of 235 disruptions to ghrelin signalling in early life (Steculorum et al, 2015). 236…”

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Hormonal and nutritional regulation of postnatal hypothalamic development

Sominsky

Jasoni

Twigg

et al. 2018

Journal of Endocrinology

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The hypothalamus is a key centre for regulation of vital physiological functions, such as appetite, stress responsiveness and reproduction. Development of the different hypothalamic nuclei and its major neuronal populations begins prenatally in both altricial and precocial species, with the fine tuning of neuronal connectivity and attainment of adult function established postnatally and maintained throughout adult life. The perinatal period is highly susceptible to environmental insults that, by disrupting critical developmental processes, can set the tone for the establishment of adult functionality. Here, we review the most recent knowledge regarding the major postnatal milestones in the development of metabolic, stress and reproductive hypothalamic circuitries, in the rodent, with a particular focus on perinatal programming of these circuitries by hormonal and nutritional influences. We also review the evidence for the continuous development of the hypothalamus in the adult brain, through changes in neurogenesis, synaptogenesis and epigenetic modifications. This degree of plasticity has encouraging implications for the ability of the hypothalamus to at least partially reverse the effects of perinatal mal-programming.

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Section: Perinatal Programming Of Metabolic Circuitry 161mentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Hormonal and nutritional regulation of postnatal hypothalamic development

Sominsky

Jasoni

Twigg

et al. 2018

Journal of Endocrinology

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“…Ghrelin is also produced in the mammary gland, it can influence glucose metabolism, energy balance, gastrointestinal motility, gastric acid secretion, and cardiovascular and immune system function [27]. It can stimulate food intake in rats and humans.64 by acting primarily on the accurate nucleus of the hypothalamus [28].…”

Section: Ghrelinmentioning

confidence: 99%

Bioactive Factors in Breast Milk: The Impact on Nutritional Programming of Childhood Obesity

Mao¹

2017

BJSTR

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“…Recently, Steculorum et al reported that neonatal ghrelin programs development of hypothalamic feeding circuits (58). Direct exposure of postnatal hypothalamic neuronal explants to ghrelin blunted axonal growth and blocked the neurotrophic effect of the adipocyte-derived hormone leptin.…”

Section: Actions On Dietary Regulationmentioning

confidence: 99%

Physiological Functions and Pathology of Ghrelin

Sato¹

2015

AJLS

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Abstract:Ghrelin is a peptide hormone made up of 28 amino acid residues; the N-terminal serine 3 residues is modified by octanoic acid, a medium-chain fatty acid. Ghrelin is mainly secreted by the stomach and has various effects, including growth hormone release, hyperphagia, lipid accumulation, suppression of insulin secretion, and hypotensive effects. Most of these physiological effects are indispensable functions for the maintenance of homeostasis and contribute to the onset and promotion of metabolic syndrome. Accordingly, it is important to combine etiological and pathological understanding based on the biochemistry and physiology of ghrelin, which has a characteristic structure. In this manuscript, after presenting biochemical information on ghrelin, we provide an outline of its physiological function.

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Neonatal ghrelin programs development of hypothalamic feeding circuits

Cited by 135 publications

References 56 publications

Hormonal and nutritional regulation of postnatal hypothalamic development

Hormonal and nutritional regulation of postnatal hypothalamic development

Bioactive Factors in Breast Milk: The Impact on Nutritional Programming of Childhood Obesity

Physiological Functions and Pathology of Ghrelin

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