Ghrelin, energy balance, and weight in infants: the chicken or the egg?

Ghrelin, a novel peptide consisting of 28 amino acids was first characterized in 1999 (1), is produced predominantly in the stomach, and is now also known to be present in the hypothalamus, the anterior pituitary gland, testis and ovarian tissue and in a variety of tumors (2–4). Ghrelin has been shown to stimulate appetite, gastric motility and acidity in adults and via these mechanisms may also act to regulate energy balance. The effects of ghrelin on appetite appear to be due to its modulation of hypothalamic neuropeptide Y (5). However, ghrelin also likely plays a major role in the modulation of somatic growth via the secretion of pituitary growth hormone (GH). It is now well understood that ghrelin functions in this latter respect by attaching to the growth hormone secretagogue receptor (GHS-R) (1,6), thereby stimulating GH secretion. Further studies (7) have now also shown that in addition to acting upon secretion of stored hormone, ghrelin also stimulates GH gene expression directly, also via the GHS-R. The literature on the effects and biochemistry of ghrelin has grown steadily since its discovery and, to date, a literature search using PubMed (8) produced a total of 1,315 references in which the term ‘‘ghrelin’’ appeared. Because of the link between ghrelin and growth modulating factors, such as GH, Insulin-Like Growth Factor-I (IGF-I) and leptin, a number of investigators have concentrated on the potential for ghrelin to serve as a modulator during the period of rapid growth associated with early infancy (9–12). In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Savino et al. (13) have presented data from their work in a cross sectional study at the University of Turin, Italy, that when data from the study population were pooled, serum concentrations of ghrelin from babies in their first year of life rise with advancing age, with no gender differences noted. Thus, in this cross sectional study, the larger the infant at the time of sampling, the higher the ghrelin concentration. It is not clear whether this finding is based predominantly on the effects of advancing age in general on ghrelin concentration, as this correlation has been documented previously by others (11,12), or whether maturation of the ghrelin-GH axis is an additional independent variable. In term babies, birth weight seems generally not to correlate with ghrelin concentration unless there has been significant growth restriction in utero, in which case cord blood levels have been found to be markedly above those of babies normally grown (9,14). By one year of age, however, these differences are no longer apparent, (15) perhaps due to catch up growth. However, Savino, et al have also shown that although ghrelin concentrations can be directly correlated with postnatal weight and length at time of collection in both breast fed (BF) and formula fed (FF) babies, weight gain from birth correlates negatively with serum ghrelin levels in the BF group but not at all in the FF group. This constitutes an extension of a previous study from birth through 4months of age, in which these authors (16) also found that FF babies had higher serum ghrelin levels during this period, but that these differences did not persist. The negative correlation between total weight gain in the first year of life and ghrelin level in only the BF group is intriguing, particularly since ghrelin is thought This editorial accompanies an article. Please see Savino F, Liguori SA, Fissore MF, et al. Serum ghrelin concentration and weight gain in healthy term infants in the first year of life. J Pediatr Gastroenterol Nutr 2005;41:653–659.