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PubMed2006

Ghrelin receptor mutations--too little height and too much hunger.

The ghrelin receptor is known from in vitro studies to signal in the absence of the hormone ghrelin at almost 50% of its maximal capacity. But, as for many other 7-transmembrane receptors, the in vivo importance of this ligand-independent signaling has remained unclear. In this issue of the JCI, Pantel et al. find that a natural mutation in the ghrelin receptor, Ala204Glu, which is associated with a selective loss of constitutive activity without affecting ghrelin affinity, potency, or efficacy, segregates in 2 families with the development of short stature (see the related article beginning on page 760). By combination of the observations from this study with those related to the phenotype of subjects carrying another natural ghrelin receptor mutation, Phe279Leu, having identical molecular-pharmacological properties, it is proposed that selective lack of ghrelin receptor constitutive signaling leads to a syndrome characterized not only by short stature, but also by obesity that apparently develops during puberty.

Amino Acid Substitution↗
PubMed2006

Ghrelin stimulates gastric emptying and hunger in normal-weight humans.

CONTEXT: Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. MAIN OBJECTIVE: The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion in normal volunteers. DESIGN: This was a randomized, double-blind, crossover study. SUBJECTS: Subjects included normal human volunteers and patients with GH deficiency. INTERVENTION: Intervention included saline or ghrelin (10 pmol/kg.min) infusion for 180 min after intake of a radioactively labeled omelette (310 kcal) or GH substitution in GH-deficient patients. MAIN OUTCOME MEASURES: Measures consisted of gastric empty-ing parameters and postprandial plasma levels of ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY, and motilin. RESULTS: The emptying rate was significantly faster for ghrelin (1.26 +/- 0.1% per minute), compared with saline (0.83% per minute) (P < 0.001). The lag phase (16.2 +/- 2.2 and 26.5 +/- 3.8 min) and half-emptying time (49.4 +/- 3.9 and 75.6 +/- 4.9 min) of solid gastric emptying were shorter during ghrelin infusion, compared with infusion of saline (P < 0.001). The postprandial peak in plasma concentration for cholecystokinin and glucagon-like peptide-1 occurred earlier and was higher during ghrelin infusion. There was no significant effect of ghrelin on plasma motilin or peptide YY. There was no difference in gastric emptying before and after GH substitution. CONCLUSION: Our results demonstrate that ghrelin increases the gastric emptying rate in normal humans. The effect does not seem to be mediated via GH or motilin but may be mediated by the vagal nerve or directly on ghrelin receptors in the stomach. Ghrelin receptor agonists may have a role as prokinetic agents.

Adult↗
PubMed2006

Does hunger influence judgments of female physical attractiveness?

To account for male preferences for female body weight following a consistent socio-economic pattern, Nelson and Morrison (2005) proposed a social-cognitive model based on the individual experience of resource scarcity. We replicated their studies showing that calorific dissatisfaction can influence preference for female body weight using a different dependent variable, namely photographic stimuli of women with known body weight and shape. Using this revised methodology, we found that operationalized intra-individual resource scarcity affects preferences for body weight: 30 hungry male participants preferred figures with a higher body weight and rated as more attractive heavier figures than 31 satiated male participants. Hungrier men were also less likely to be influenced by cues for body shape, supporting extant cross-cultural studies on female physical attractiveness. These findings corroborate those of Nelson and Morrison (2005) and are discussed in terms of how cultural contexts shape individual psychological experience as predicted by the theory of mutual constitution.

Adult↗
PubMed2005

Hunger-satiety signals in patients with Graves' thyrotoxicosis before, during, and after long-term pharmacological treatment.

UNLABELLED: Patients with Graves' thyrotoxicosis lose weight despite increased appetite and food intake, thus suggesting a disturbed balance between energy intake and expenditure. Underlying mechanisms are not fully elucidated. The objective of this study was to investigate whether hormonal factors, known to affect hunger/satiety, change significantly over time as pharmacological treatment turns hyperthyroidism into euthyroidism. For that purpose 11 patients with Graves' thyrotoxicosis were given thiamazole and l-thyroxine for 18-20 mo. They were investigated on three occasions: Test 1: before pharmacological therapy; Test 2: during medication; Test 3: a few months after conclusion of the pharmacological treatment. Sixteen healthy subjects were also investigated for comparison. The participants were fasted overnight. Blood samples for determination of plasma glucose and serum concentrations of free T3 and T4, TSH, albumin, cortisol, insulin, GH, IGF-1, IGFBP-1, leptin, and ghrelin were drawn in the morning from an antecubital vein. Laboratory data obtained in test 1 were statistically compared with those in tests 2 and 3. The study showed that the free T3 level declined from 42.8 +/- 4.3 pmol/L in test 1 to 6.0 +/- 0.8 pmol/L in test 2 (85 +/- 2% decline), and 5.5 +/- 0.3 pmol/L in test 3 (86 +/- 2% decline). The free T4 level fell concomitantly from 65.2 +/- 4.8 to 16.6 +/- 1.7 and 14.4 +/- 1.2 pmol/L. The glucose level was significantly higher during hyperthyroidism (test 1) than during euthyroidism (tests 2 and 3), whereas cortisol, insulin, GH, IGF-1, and leptin levels were similar. The IGFBP-1 level was initially high (48.8 +/- 8.5 microg/L in test 1), but with a relative decline in free T3 of 85 +/- 2% (test 2) the IGFBP-1 level declined by 34 +/- 13%, and with a free T3 decline of 86 +/- 2% (test 3) the binding protein fell by 39 +/- 29%. This brought about increased IGF-1 bioavailability as reflected by a rising IGF-1/IGFBP-1 ratio from 5.1 +/- 1.1 to 13.8 +/- 2.9 (p < 0.01). The ghrelin level was low (2454 +/- 304 ng/L) in test 1. It increased to 3127 +/- 397 ng/L in test 2 (p < 0.05), and to 3348 +/- 279 ng/L in test 3 (p < 0.01). CONCLUSION: Both ghrelin secretion and IGF-1 bioavailability are low in patients with untreated thyrotoxicosis, but increase markedly as pharmacotherapy makes them euthyroid. These metabolic changes may be caused by the transition of hyperthyroidism into euthyroidism rather than by the pharmacotherapy per se, since the metabolic changes prevailed also in the posttreatment period.

Adolescent↗
PubMed1987

Sexual activity increases plasma concentrations of cholecystokinin octapeptide and offsets hunger in male rats.

Male rats deprived of food for 48 h ignored food pellets immediately after ejaculating with a sexually receptive female rat as did males tested 5 min after i.p. injection of 5 micrograms cholecystokinin octapeptide (CCK-8) or males which had consumed food pellets for 1 h. The concentration of CCK-8 in plasma was increased to comparable levels (10.1 +/- 3.8 (S.E.M.); 11.3 +/- 3.7 and 7.2 +/- 0.5 pmol/l respectively, compared with 1.2 +/- 0.3 pmol/l for NaCl-injected controls) under each of these conditions, whereas the concentration of gastrin increased only after food consumption (18.4 +/- 3.8; 17.7 +/- 5.4 and 54.3 +/- 7.0 pmol/l respectively, compared with 21.5 +/- 2.1 pmol/l for NaCl-injected controls). The effect of ejaculation on the latency to starting to eat was partially reversed by i.p. injection of 50 mg of the CCK-8 antagonist proglumide, but neither treatment with proglumide or CCK-8 nor consumption of food affected the display of sexual behaviour. The results support the suggestion that CCK-8 is a 'satiety peptide' in the rat.

Animals↗
PubMed1992

The politics of hunger: when science and ideology clash.

In recent years the WIC program, a federal nutrition program for poor mothers and babies, has become a major playing field for ideological forces hoping to shape public opinion and Congressional action on matters of domestic social policy. WIC's highly positive benefits have been distorted, research results from its scientific evaluation altered by high-level federal officials, and its public support undermined by an academic spokesman with ties to the White House and a stated desire to kill the program. While strong bipartisan support on Capitol Hill makes it likely that WIC will survive and even grow, distortion of its record provides insight into how ideological forces contaminate the well of reasoned discourse for their preconceived ends.

Female↗