SummaryLeptin and ghrelin are two hormones that have been recognized to have a major influence on energy balance. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. As a growing number of people suffer from obesity, understanding the mechanisms by which various hormones and neurotransmitters have influence on energy balance has been a subject of intensive research. In obese subjects the circulating level of the anorexigenic hormone leptin is increased, whereas surprisingly, the level of the orexigenic hormone ghrelin is decreased. It is now established that obese patients are leptin-resistant. However, the manner in which both the leptin and ghrelin systems contribute to the development or maintenance of obesity is as yet not clear. The purpose of this review is to provide background information on the leptin and ghrelin hormones, their role in food intake and body weight in humans, and their mechanism of action. Possible abnormalities in the leptin and ghrelin systems that may contribute to the development of obesity will be mentioned. In addition, the potentials of leptin and ghrelin as drug targets will be discussed. Finally, the influence of the diet on leptin and ghrelin secretion and functioning will be described.

Already in the first week of caloric restriction in obese postmenopausal women, various favourable metabolic changes occur before clinically relevant weight loss is achieved. Activity in the amygdala region and correlations of metabolic factors with activity in brain areas involved in food reward processing differ substantially before and after weight loss.

Regional brain activity in 15 healthy, normal weight males during processing of visual food stimuli in a satiated and a hungry state was examined and correlated with neuroendocrine factors known to be involved in hunger and satiated states. Two functional Magnetic Resonance Imaging (fMRI) sessions were performed with a one week interval, after overnight fasting or 1 hour after a standardized meal. Blood samples and appetite assessment were obtained after each fMRI session. Main effects of processing food versus non-food stimuli were observed in the ventral visual stream, including the fusiform gyrus and hippocampal areas bilaterally, significantly more in the fasting state. Leptin concentration correlated negatively with activity in the left hippocampal area and right insula during the satiation condition. A positive correlation between ghrelin and "thought of food" hunger scores were found. The positive correlation between ghrelin and food related activation in the insula areas and the right hippocampus during fasting did not reach significance. Conclusion:The increased activation of food vs non-food pictures in the ventral visual stream reflects increased salience of food pictures when subjects are hungry. Leptin was associated with activations in areas involved in processing of new information and emotion.

Human growth hormone (GH) is well established as a treatment for growth hormone deficiency. Recently, a new liquid GH formulation (Norditropin SimpleXx®) has become available that does not require reconstitution before subcutaneous self-administration with a new delivery system (NordiPen™) and an optional auto-injector (NordiPenmate™). In this study the acceptability and tolerability of and compliance with the liquid formulation were investigated DESIGN AND PATIENTS: An open 6-week multicentre trial in 53 patients, including adults and children, was performed in The Netherlands. Acceptability and tolerability of the liquid GH formulation were assessed by questionnaires and compliance by both questionnaires and re-collection of GH cartridges MAIN OUTCOME MEASURES AND RESULTS: The mean daily dosage of GH was 0.24 mg/m (0.03 to 0.82 mg/m) in adults and 1.13 mg/m (0.65 to 1.77 mg/m) in children. Most patients (91% of adults and 89% of children) preferred to continue on the new GH formulation rather than the previously used formulation. This was mainly due to the easier and less time-consuming procedure and the good tolerance of the drug. Self-reported compliance also improved, but this could not be proven due to poor return of study cartridges CONCLUSIONS: The use of the liquid GH formulation Norditropin SimpleXx® with the NordiPen™ device and optional use of the NordiPenmate™ device was well accepted by both adults and children. This was mainly due to the avoidance of reconstitution and the ease of handling of the injection device.

In this large cohort of community dwelling older people, we observed lower serum IGF-I levels in the higher age categories. A low serum IGF-I was associated with significantly lower measurements of body composition, such as BMI, skinfolds and WHR. These results do not support previous findings that high IGF-I levels are favourable for a healthy body composition in community dwelling older people.

(1) Background: Prader–Willi syndrome (PWS) is characterized by hyperphagia, resulting in morbid obesity if not controlled. The primary aim of this study was to investigate whether PWS patients show altered activation of brain areas involved in hunger. As a secondary objective, we assessed whether there is an association between these brain areas and several endocrine and metabolic factors in the fasting state. (2) Methods: 12 PWS adults and 14 healthy controls (siblings) performed a food-related experimental task after an overnight fast while brain activation in regions of interest was measured by functional MRI. (3) Results: In controls, significantly more activation was found in the left insula (p = 0.004) and the bilateral fusiform gyrus (p = 0.003 and 0.013) when the individuals were watching food as compared to non-food pictures, which was absent in PWS patients. Moreover, in PWS adults watching food versus non-food pictures a significant negative correlation for glucose and right amygdala activation (p_fwe = 0.007) as well as a positive correlation for leptin and right anterior hippocampus/amygdala activation (p_fwe = 0.028) was demonstrated. No significant associations for the other hormonal and metabolic factors were found. (4) Conclusions: PWS individuals show aberrant food-related brain activation in the fasting state. Leptin is associated with activation within the neural motivation/reward circuitry, while the opposite is true for glucose.

The pituitary reaction on CRH and GHRH was not significantly changed by various blood glucose levels.

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