Dynamic Changes in Serum Leptin Concentrations during the Fetal and Neonatal Periods

Matsuda, Junko; Yokota, Ichiro; Iida, M.; Murakami, Takashi; Yamada, Masayo; Saijo, Takahiko; Naito, Etsuo; M, Ito; Shima, Kenji; Kuroda, Yasuhiro

doi:10.1203/00006450-199901000-00012

Cited by 71 publications

(62 citation statements)

References 25 publications

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“…In contrast to the findings regarding leptin concentrations [7,8], considerable levels of active and total ghrelin were detected in premature newborns.…”

Section: Resultscontrasting

confidence: 49%

Concentration of the n-Octanoylated Active Form of Ghrelin in Fetal and Neonatal Circulation

Yokota

Kitamura

Hosoda³

et al. 2005

Endocr J

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Abstract. The octanoylation of Ser3 is essential for the biological function of ghrelin. We examined the concentrations of the n-octanoylated active-form ghrelin in cord and neonatal blood using an RIA system that specifically recognized n-octanoylated ghrelin, as well as a system that measured the total ghrelin concentration. Plasma levels of active ghrelin in cord blood ranged from 7.7 to 38.4 pmol/l and correlated excellently with those of total ghrelin (r = 0.81, p<0.0001). The active ghrelin/total ghrelin (A/T) ratio ranged from 0.038 to 0.12 (median 0.072). The active ghrelin concentrations negatively correlated with birth body weight (r = -0.34, p = 0.01) and IGF-1 concentrations (r = -0.40, p = 0.003), but did not correlate with growth hormone (GH) concentrations. A considerable level of active ghrelin was detected in premature newborns. Venous cord blood samples showed a significantly higher active ghrelin concentration (p = 0.03) and A/T ratio (p = 0.01) than those in the artery. In neonatal blood, active ghrelin concentrations ranged from 4.6 to 22.6 pmol/l and the A/T ratio ranged from 0.02 to 0.081. These results demonstrate the existence of active-form ghrelin in fetal and neonatal circulation and may suggest the energy supply-dependent regulation of ghrelin expression/secretion in utero. GHRELIN is a 28-amino acid peptide that contains an n-octanoyl modification of Ser3 [1,2]. This modification is essential for the biological functions of this hormone such as in GH-secretion and appetite stimulation, since the octanoylation of Ser3 is necessary to bind to type 1a growth hormone secretagogue receptor (GHSR1a) [1,3]. Measurement of this active-form ghrelin is important for evaluating the regulation and physiological roles of circulating ghrelin under various conditions in humans. However, this octanoylated active-form ghrelin is unstable in blood and easily changes to the des-octanoyl form during sample collection and storage [4]. This makes it difficult to evaluate the mechanism of octanoylation and the significance of its regulation under physiological and pathological states. We previously reported cord and neonatal blood ghrelin concentrations using a radioimmunoassay (RIA) system that measured total (both octanoyl and desoctanoyl) ghrelin concentrations [5]. Total ghrelin concentrations in cord blood correlated negatively with anthropometric and hormonal parameters that represent the nutritional status of fetuses, which suggested that fetal ghrelin concentrations were regulated in a fetomaternal energy transport-dependent manner. However, the presence of n-octanoylated active-form ghrelin during the perinatal period and its relation to desoctanoylated ghrelin has not been well examined. Thus, measurement of active-form ghrelin concentrations in the fetal and neonatal circulation is very important for better understanding the role of ghrelin during this period [6].In the present study, we measured n-octanoylated active-form ghrelin concentrations in cord and neonatal blood using an octanoylated ...

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“…In contrast to the findings regarding leptin concentrations [7,8], considerable levels of active and total ghrelin were detected in premature newborns.…”

Section: Resultscontrasting

confidence: 49%

Concentration of the n-Octanoylated Active Form of Ghrelin in Fetal and Neonatal Circulation

Yokota

Kitamura

Hosoda³

et al. 2005

Endocr J

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“…In humans (19) and rodents (20), serum leptin can be detected at birth and then it undergoes a rapid decline. These changes may reflect alterations in hormonal and nutritional status (19) during the early neonatal period.…”

Section: Discussionmentioning

confidence: 99%

Leptin Reduces Body Weight Gain in Neonatal Rats

Yuan

Attele²,

Zhang³

et al. 2000

Pediatr Res

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Leptin (OB protein) elicits a neuroendocrine response to starvation and states of nutritional abundance to stabilize the proportion of body fat. Leptin has dramatic effects on food intake and energy expenditure in adult and juvenile rodents. However, whether the neonatal period is associated with the development of an effective leptin feedback system is still not known. In this study, we evaluated the effects of peripherally administered leptin on body weight changes in neonatal rats during the early suckling period (from birth to 10 d). Our results show that daily i.p. injections of leptin (0.3 g/g and 1.0 g/g) to neonatal rats led to a significant reduction in weight gain over 10 d compared with the control group (p Ͻ 0.01 and p Ͻ 0.01, respectively). Concomitant with a reduction in weight gain, retroperitoneal fat pad weight also significantly decreased in the leptin-treated group. Our data indicate that the potential for energy balance regulation by leptin occurs in the first day after birth. In addition, we also observed that 3 d after discontinuing leptin treatment, the body weight as well as the fat pad weight of leptin-treated pups returned to the control level. Our results demonstrate that leptin reduces body weight gain in neonatal rats. Leptin, the secreted product of the obese (ob) gene, regulates food intake and energy expenditure (1, 2). Leptin may increase energy expenditure by enhancing systemic (3) and brown adipose tissue glucose utilization (4). Thus far, adipose tissue (5) as well as the stomach (6) have been identified as sites of leptin synthesis. Leptin acts as a link in the feedback loop between adipose tissue and satiety centers in the hypothalamus, resulting in a decrease in appetite and an increase in energy expenditure (5, 6). However, it is also possible that sources of leptin other than adipose tissue play a similar role. For example, the epithelium of the gastric fundus and gastric glands not only synthesize and store leptin, but also secrete leptin in response to food intake (7). Arterially injected leptin increases gastric vagal nerve activity (8), and these afferent inputs link nutrient-related events in the gastrointestinal tract to the CNS areas that mediate the control of food intake (9, 10). We recently observed that leptin applied to the gastric mucosa increases neuronal activity in the nucleus tractus solitarius of the brain stem, the first relay station of autonomic afferent inputs (11).There is evidence that leptin regulates body weight during the postnatal period (12, 13). However, in young rodents, unlike in adults, leptin decreases body weight gain via increasing energy expenditure by varying the metabolic rate (13). In suckling pups (from birth to 21 d), because food intake is restricted by the maternal milk supply, the energy expended for thermoregulation limits the energy left for growth and fat deposition (14). Moreover, endogenous leptin levels of postnatal rats correspond to changes in dietary fat intake. Trottier et al. (15) reported that suckling rat pups fe...

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“…It is thus not unexpected that leptin administration has such a marked effect on this process (23) and related processes (24,25) , which are not seen when given to the lategestation fetus or neonatal sheep (26,27) . Indeed, there is no postnatal leptin surge in either sheep (28) or man (29) . Nephron development occurs primarily after birth, as does brown fat, which in sheep and man was originally thought to be completely lost in the postnatal period (30) , but is retained throughout the life cycle in the rodent.…”

Section: Comparative Differences In Organ Developmentmentioning

confidence: 99%

Nutritional models of the developmental programming of adult health and disease

Symonds

Budge

2009

Proc. Nutr. Soc.

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The ability to not only replicate but also extend the findings from both historical epidemiological studies and contemporary cohorts of the developmental programming of later disease are critical if the mechanisms by which early diet impacts on later disease are to be fully understood. To date, a plethora of models have been established, with the range including global changes in dietary input, imbalanced diets and diets deficient in single nutrients. Key factors in translating these findings to the human situation are the pronounced differences in the relative growth and development between large and small mammals from the time of conception through pregnancy, lactation and weaning. This disparity is reflected in the very different nutritional requirements between species and the substantial divergence between rodents and large animals in the ontogeny of many of the organ systems that are nutritionally regulated. For example, hypothalamic circuitry is much more developed in species with a long gestation and offspring are born with a mature hypothalamic-pituitary axis in sheep and man compared with mice and rats. Similarly, nephron number is established towards the end of gestation in large mammals compared with the lactational period in rats. These types of differences will impact on the ability of individual and combined nutritional interventions to reset developmental processes, and may be further compounded by the gender of a fetus. The challenge for future work in this exciting and dynamic area of research is to utilise these marked comparative differences to generate imaginative nutritional interventions in order to improve the viability, health and well-being of the offspring.

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Dynamic Changes in Serum Leptin Concentrations during the Fetal and Neonatal Periods

Cited by 71 publications

References 25 publications

Concentration of the n-Octanoylated Active Form of Ghrelin in Fetal and Neonatal Circulation

Concentration of the n-Octanoylated Active Form of Ghrelin in Fetal and Neonatal Circulation

Leptin Reduces Body Weight Gain in Neonatal Rats

Nutritional models of the developmental programming of adult health and disease

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