Alfred C. K. Wong

Immunoreactive Ghrelin in human cord blood : Relation to anthropometry, leptin, and growth hormone

Background Ghrelin is secreted by the stomach, the hypothalamus, and the placenta in humans and has growth hormone–secreting and orexigenic properties. Leptin is secreted mainly by the adipocyte, plays a major role in energy balance, and reflects fat mass in infants as well as adults. Leptin and ghrelin central effects are mediated, at least partly, through the neuropeptide Y/Y1 receptor pathway in the hypothalamus. Methods We determined whether ghrelin is also present in the fetus and investigated its relationship to leptin, growth hormone, birth weight, and calf and abdominal circumferences in 90 full-term neonates. Results Immunoreactive ghrelin was detected in all cord samples (mean ± SD, 187 ± 88 pmol/L; range, 66—594 pmol/L). In contrast to leptin, ghrelin concentrations of boys and girls were not statistically different. In female neonates, ghrelin is inversely correlated with anthropometric measures. In male neonates, ghrelin is positively correlated with leptin and negatively with growth hormone. Conclusion The presence of significant ghrelin concentrations in all neonates before the first feeding is intriguing. Unlike the fairly constant concentrations and effects of leptin over the short term, the wide variability of ghrelin concentrations observed in newborns raises the possibility that ghrelin secretion causes short-term changes in feeding behavior. We suggest that ghrelin may play a physiologic role in the initiation of feeding.

Obestatin, acylated and total ghrelin concentrations in the perinatal rat pancreas

Background: Ghrelin and obestatin are encoded by the preproghrelin gene and originate from posttranslational processing of the preproghrelin peptide. The fetal rat pancreas contains acylated and desacylated ghrelin peptides, as well as growth hormone secretagogue receptor -1a mRNA. Acylated ghrelin inhibits insulin secretion. We investigated the plasma and tissue ontogeny of ghrelin and obestatin in the rat. Methods: We measured obestatin and acylated and total ghrelin concentrations in plasma, pancreas and stomach from rat fetuses (F20) and neonates at postnatal day (PN) 1, 6, 12 and 21). Results: Overall, obestatin concentrations were markedly lower than total ghrelin concentrations. In plasma, total ghrelin concentrations decreased abruptly after birth (p < 0.05), contrasting with a 3 times increase in the concentration of acylated ghrelin between F20 and PN1 (p < 0.05). In pancreas, total ghrelin and obestatin concentrations decreased progressively from PN1 to PN21 but acylated ghrelin concentrations increased 6–7 times from F20 (18 [6] pg/ml) to PN6 (122 [59] pg/ml). The percent of acylated ghrelin increased from 1.8 (0.6) at F20 to 39.7 (13.0) % of total ghrelin immunoreactivity at PN12 (p < 0.05). There were significant positive correlations between postnatal obestatin, acylated or total ghrelin and insulin concentrations in the pancreas (all p < 0.02, r2 > 0.21) and between postnatal total ghrelin and obestatin (in pancreas, r2 = 0.37) or acylated ghrelin (in stomach, r2 = 0.27) (p < 0.001). Conclusion: Ghrelin and obestatin are present in the perinatal pancreas where they could potentially affect insulin secretion.

GLP-1 and Appetite Responses to a Meal in Lean and Overweight Adolescents Following Exercise

Objective: Increased physical activity is an integral part of weight loss programs in adolescents. We prospectively investigated the effects of exercise on glucagon‐like peptide‐1 (GLP‐1) concentrations and on appetite markers.

Ghrelin is suppressed by glucagon and does not mediate glucagon-related growth hormone release

Background:Glucagon stimulation is routinely used as a provocative test to assess growth hormone (GH) sufficiency in pediatrics. Ghrelin also markedly stimulates GH secretion. Because glucagon stimulates the promoter of the ghrelin gene in vitro as well as ghrelin secretion by the perfused rat stomach, we sought todetermine whether ghrelin mediates glucagon-induced GH secretion. Methods: We compared ghrelin, GH, insulin and glucose responses following administration of 0.03 mg/kg intravenously (iv; max. 1 mg) and 0.1 mg/kg intramuscularly (im; max. 2 mg) of glucagon in two groups (n = 10–11/group) of GH-sufficient children. We also measured ghrelin before and 6 min after iv administration of 1 mg glucagon in 21 adult subjects. Results: In children, glucagon caused a 26% decrease in ghrelin and a 72% increase in glucose concentrations that were independent of the dose or administration route of glucagon. In contrast, the insulin response was 2–3 times higher following administration of 0.1 mg/kg im compared to 0.03 mg/kg of glucagon iv. There was a significant correlation between the maximum decrease in ghrelin and increases in glucose (p = 0.03) but not in insulin. There was a significant correlation between ghrelin and GH area under the curve after controlling for the dose of glucagon (p = 0.03) but not for the maximum increase in glucose.In normal adults, glucagon administration caused a 7% decrease in ghrelin concentrations after 6 min (p = 0.0002). Conclusion: Ghrelin does not play a causal role in the GH response to pharmacological glucagon administration, which suppresses ghrelin levels starting a few minutes after injection.

Umbilical cord ghrelin concentrations in Asian and Caucasian neonates.

Objectives: To compare the relationship between cord plasma ghrelin and growth hormone (GH) concentrations and birth weight in Asian and Caucasian neonates. Methods: We measured umbilical cord ghrelin and GH concentrations in 180 full-term newborns [4 groups of 45 according to ethnicity (Caucasian/Asian) and sex]. Results: Ghrelin was detectable in all umbilical cord samples (mean ± SD: 611 ± 267, range 193–2,010 pg/ml). There was no significant difference in ghrelin concentrations between Asian and Caucasian male or female neonates. In contrast, GH values were significantly affected by sex (p = 0.001) and ethnicity (p = 0.006). Except for a weak (r = –0.33, p < 0.03) negative correlation between ghrelin and GH in male Caucasian neonates, ghrelin and GH concentrations were independent. Conclusions: Umbilical cord concentrations of ghrelin, a potent orexigenic and GH stimulatory agent, are similar in Caucasian and Asian newborns, suggesting that ghrelin does not play a causal role in the differences in body composition and GH metabolism observed in these neonates.

Different relationship between anthropometric markers and umbilical cord plasma leptin in Asian and Caucasian neonates.

The leptin to fat ratio early in life could contribute to fixing the set point of leptin feedback at the hypothalamic level. Subjects from Asian and Caucasian ethnicities differ in body composition. We tested the hypothesis that anthropometric markers and their relationship to umbilical cord leptin, cortisol and cortisone, DHEAs and oestriol differed between Caucasians and Asians at birth. Birthweight, length, arm, calf and abdominal circumferences, scapular, triceps, quadriceps and abdominal skinfolds were measured in 180 healthy, full-term newborns of Asian and Caucasian ethnicities. Leptin and steroid hormone concentrations were determined in umbilical cord plasma. There was a significant difference in the slope of the regression between leptin and birthweight (p = 0.03) and calf circumference (p = 0.05) between male Caucasian and Asian neonates. In contrast, in female neonates, there was no significant difference (p = 0.099 and p = 0.07 for birthweight and calf circumference, respectively). In addition, while the slopes of the regression plots were not affected by gender in Asian newborns, there was a significant difference between male and female Caucasian newborns (p = 0.006 and p = 0.002 for birthweight and calf circumference, respectively). There was no significant correlation between cord leptin concentrations or anthropometric markers and steroid hormone concentrations. In conclusion, gender and ethnic differences in the relationship between leptin and anthropometric markers are detectable at birth between Asians and Caucasians, two ethnic groups that have been demonstrated to have different body compositions later in life. This may represent the first clinical evidence of a difference in leptin regulation between these two ethnic groups.

Reliability of the AccuSens Taste Kit© in patients with eating disorders

Zinc deficiency is a putative risk factor for anorexia nervosa (AN). Detecting zinc deficiency may therefore be important in treatment. However, serum zinc is not a good measure of total body zinc. An alternative test for zinc deficiency is taste testing because zinc deficiency is known to impair taste (dysgeusia). To determine whether taste testing could be used in this way, we measured the reliability of the only commercially available taste test in 16 patients with eating disorders. The results were analyzed graphically and with the kappa statistic (K). The taste test was found to be unreliable and should not be used to determine zinc status.