Elevated Umbilical Cord Ghrelin Concentrations in Small for Gestational Age Neonates

Farquhar, Juliet; Heiman, Mark L.; Wong, Alfred C. K.; Wach, Richard; Chessex, Philippe; Chanoine, Jean‐Pierre

doi:10.1210/jc.2003-030265

Cited by 101 publications

(110 citation statements)

References 32 publications

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“…This accords with human data, which failed to show any difference between IUGR and normal infants (Kyriakakou et al, 2009). Others, however, demonstrated higher ghrelin levels in SGA neonates (Farquhar et al, 2003). Hence, the specific role of ghrelin in perinatal growth remains unclear.…”

Section: Discussionsupporting

confidence: 88%

Ghrelin in the gastrointestinal tract and blood circulation of perinatal low and normal weight piglets

Willemen

Vos

Huygelen

et al. 2013

Animal

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Ghrelin, the 'hunger' hormone, is an endogenous growth hormone secretagogue that exerts a wide range of physiological functions. Its perinatal presence suggests that ghrelin might be involved in growth and metabolism processes during intrauterine and postnatal life. Intrauterine growth-restricted (IUGR) neonates have altered endocrine and metabolic pathways because of malnutrition during foetal development. These changes might include an altered gastrointestinal presence of ghrelin cells (GCs). As ghrelin is mainly secreted by the stomach, this altered presence might be reflected in its serum concentrations. Smallfor-gestational age (SGA) pigs appear to be a natural occurring model for IUGR children. Therefore, the first aim of this study was to investigate the presence of gastrointestinal GCs expressing active ghrelin in normal weight (NW) foetal and postnatal piglets compared with their SGA littermates using immunohistochemical analysis in combination with stereological methods. Second, total ghrelin serum concentrations of these piglets were analysed with a porcine radioactive immunoassay. In addition, the growth of the gastric pars fundica in the NW and SGA piglets was analysed stereologically. Corresponding with humans and rats, it was shown that opened-and closed-type immunoreactive GCs are distributed along the entire gastrointestinal tract of the perinatal NW and SGA piglets. However, in contrast to the rat's stomach, the porcine GCs do not disperse from the glandular base to the glandular neck during perinatal development. Furthermore, stereological analysis demonstrated that the NW neonates have a higher amount of gastric cells expressing active ghrelin compared with the SGA piglets that could result in higher milk consumption during the neonatal period. This finding is, however, not reflected in total serum ghrelin levels, which showed no difference between the NW and SGA piglets. Moreover, the stereological volume densities of the fundic layers demonstrate a similar growth pattern in the SGA and NW piglets.

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Section: Discussionsupporting

confidence: 88%

Ghrelin in the gastrointestinal tract and blood circulation of perinatal low and normal weight piglets

Willemen

Vos

Huygelen

et al. 2013

Animal

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“…Furthermore, total ghrelin levels were higher in SGA and had a weak but significant negative partial correlation with IGF1 levels. Together, these data suggest that ghrelin already has a functional role in late pregnancy, acting to favor a positive energy balance under fetal growth restriction, and that total ghrelin levels are regulated through a negative feedback system by fetal weight and, maybe, IGF1 (31).…”

Section: Discussionmentioning

confidence: 82%

Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism

Martos‐Moreno¹,

Barrios²,

Pipaón³

et al. 2009

European Journal of Endocrinology

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Objective: To determine the influence of gestational age and fetal growth restriction on the cord blood adipokine profile, IGF1, and ghrelin levels, and their relationship with glucose metabolism. Study design: One hundred and ninety newborns (99 preterm and 91 full term) were studied and, according to their anthropometry at birth, classified as small (SGA) or adequate for gestational age (AGA). Methods: Venous cord blood serum levels of IGF1, IGF binding protein 3 (IGFBP-3), adiponectin, resistin, leptin, soluble leptin receptor (sOB-R), tumoral necrosis factor-a, interleukin 6 (IL-6), total ghrelin, and acylated ghrelin were determined and compared between preterm and full-term, as well as between SGA and AGA, newborns. Correlations with newborn weight, gestational age, and homeostatic model assessment (HOMA) index, as an index of insulin resistance, were determined. Results: Preterm newborns had higher HOMA, sOB-R, resistin, and IL-6 and lower IGF1, IGFBP-3, leptin, and adiponectin levels than full-term newborns. SGA had lower IGF1, IGFBP-3, leptin, IL-6, and adiponectin and higher sOB-R and total ghrelin than AGA newborns. Adiponectin and HOMA showed independent positive and negative correlations with gestational age respectively, but not with neonatal weight. Birth weight was correlated positively with IGF1 and leptin levels and negatively with total ghrelin ones. Conclusions: Our findings suggest that the lack of proper acquisition of adipose tissue by the fetus either due to prematurity or to fetal growth restriction is associated with changes in the cord blood adipokine profile that may contribute to the impairment of glucose metabolism.

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“…Ghrelin concentrations in human serum have been reported to be between 0.1-2 nM (7,10,49,58,59). Although it is difficult to estimate the needed degradation efficiency to attenuate ghrelin's ''gut-brain axis'' effects on energy homeostasis, a quantitative study on ghrelin dynamics across a day in dieting obese subjects provides starting insights (10).…”

Section: Resultsmentioning

confidence: 99%

Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice

Mayorov

Amara

Chang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Obesity is a chronic, costly, and globally prevalent condition, with excess caloric intake a suspected etiologic factor. Nonsurgical treatments are modestly efficacious, and weight loss maintenance is hampered by anti-famine homeostatic mechanisms. Ghrelin, a gastric hormone linked to meal initiation, energy expenditure, and fuel partitioning, is hypothesized to facilitate weight gain and impede weight loss. Unique among known animal peptides, the serine-3 residue of ghrelin is posttranslationally acylated with an n-octanoic acid, a modification important for the peptide's active blood-brain transport and growth hormone secretagogue receptor-1 agonist activity. Pharmacological degradation of ghrelin would be hypothesized to reduce ghrelin's biological effects. To study endogenous ghrelin's role in appetite and energy expenditure, we generated antibodies that hydrolyze the octanoyl moiety of ghrelin to form des-acyl ghrelin. The most proficient antibody catalyst, GHR-11E11, was found to display a second-order rate constant of 18 M ؊ 1⅐s ؊1 for the hydrolysis of ghrelin to des-acyl ghrelin. I.v. administration of GHR-11E11 (50 mg/kg) maintained a greater metabolic rate in fasting C57BL/6J mice as compared with mice receiving a control antibody and suppressed 6-h refeeding after 24 h of food deprivation. Indirect respiratory measures of metabolism after refeeding and relative fuel substrate utilization were unaffected. The results support the hypothesis that acylated ghrelin stimulates appetite and curbs energy expenditure during deficient energy intake, whereas des-acyl ghrelin does not potently share these functions. Catalytic anti-ghrelin antibodies might thereby adjunctively aid consolidation of caloric restrictioninduced weight loss and might also be therapeutically relevant to Prader-Willi syndrome, characterized after infancy by hyperghrelinemia, hyperphagia, and obesity.hormone inactivation ͉ obesity ͉ neuropeptides A pproximately 1 billion people worldwide are overweight or obese (body mass index ϭ 25-29.9 or Ͼ30 kg/m 2 , respectively) (1), conditions associated with significant morbidity and mortality and for which new treatments are needed (2). Among recently characterized molecules implicated in energy homeostasis, ghrelin was identified in 1999 during a search for the endogenous ligand for the GH secretagogue receptor (GHSR) (ghrelin receptor), previously localized to peripheral tissues and to several CNS sites, including the arcuate nucleus and ventromedial hypothalamic nucleus (3). Human ghrelin is a 28-amino acid acylated peptide (GSS(n-octanoyl)FLSPEHQRVQQRKESKKPPAKLQPR) released mainly from endocrine cells of the stomach and upper gastrointestinal tract but also expressed in testes, kidney, pituitary, pancreas, lymphocytes, and brain (3-7). Several findings establish gastric ghrelin as an indicator of energy insufficiency and anabolic modulator of energy homeostasis (3). Ghrelin secretion is thought to stimulate food intake, slow metabolic rate, and spare lipid oxidation via central (8) and, possi...

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Elevated Umbilical Cord Ghrelin Concentrations in Small for Gestational Age Neonates

Cited by 101 publications

References 32 publications

Ghrelin in the gastrointestinal tract and blood circulation of perinatal low and normal weight piglets

Ghrelin in the gastrointestinal tract and blood circulation of perinatal low and normal weight piglets

Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism

Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice

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