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.

Gut-derived hormones, such as GLP-1, have been proposed to relay information to the brain to regulate appetite. GLP-1 receptor agonists, currently used for the treatment of type 2 diabetes (T2DM), improve glycemic control and stimulate satiety, leading to decreases in food intake and body weight. We hypothesized that food intake reduction after GLP-1 receptor activation is mediated through appetite-and reward-related brain areas. Obese T2DM patients and normoglycemic obese and lean individuals (n = 48) were studied in a randomized, crossover, placebocontrolled trial. Using functional MRI, we determined the acute effects of intravenous administration of the GLP-1 receptor agonist exenatide, with or without prior GLP-1 receptor blockade using exendin 9-39, on brain responses to food pictures during a somatostatin pancreatic-pituitary clamp. Obese T2DM patients and normoglycemic obese versus lean subjects showed increased brain responses to food pictures in appetite-and reward-related brain regions (insula and amygdala). Exenatide versus placebo decreased food intake and food-related brain responses in T2DM patients and obese subjects (in insula, amygdala, putamen, and orbitofrontal cortex). These effects were largely blocked by prior GLP-1 receptor blockade using exendin 9-39. Our findings provide novel insights into the mechanisms by which GLP-1 regulates food intake and how GLP-1 receptor agonists cause weight loss.The global rise in obesity and type 2 diabetes (T2DM) prevalence is a major public health problem (1,2). It has been hypothesized that excessive eating due to changes in central nervous system (CNS) satiety and reward responses to food underlies the development of obesity and T2DM, comparable to the role for altered CNS responses in drug addiction (3). Several studies in obese individuals have demonstrated increased CNS responses to visual food cues in areas involved in appetite and reward processing (insula, amygdala, orbitofrontal cortex [OFC], and striatum) (4-6), and this increased CNS food-cue responsiveness predicts future weight gain (7). The mechanisms underlying these alterations in CNS responses to food cues are not clear, but multiple metabolic and hormonal factors seem to be involved (8-10).Food ingestion activates the secretion of several gutderived mediators, including the incretin hormone GLP-1. GLP-1 stimulates meal-related insulin secretion, inhibits glucagon release, and delays gastric emptying, mechanisms that all contribute to its glucometabolic effects (11). In addition, several observations suggest that GLP-1 has a role in the regulation of food intake. Systemic administration of GLP-1 reduced food intake in rodent and human studies (12), and blocking the GLP-1 receptor with

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Patients with CS are at high risk of VTE, especially during active disease and after pituitary surgery. Guidelines on thromboprophylaxis are urgently needed.

BackgroundMultiple Endocrine Neoplasia type 1 (MEN1) is diagnosed when two out of the three primary MEN1-associated endocrine tumors occur in a patient. Up to 10–30 % of those patients have no mutation in the MEN1 gene. It is unclear if the phenotype and course of the disease of mutation-negative patients is comparable with mutation-positive patients and if these patients have true MEN1. The present study aims to describe and compare the clinical course of MEN1 mutation-negative patients with two out of the three main MEN1 manifestations and mutation-positive patients during long-term follow-up.MethodsThis is a cohort study performed using the Dutch MEN1 database, including > 90 % of the Dutch MEN1 population.ResultsA total of 293 (90.7 %) mutation-positive and 30 (9.3 %) mutation-negative MEN1 patients were included. Median age of developing the first main MEN1 manifestation was higher in mutation-negative patients (46 vs. 33 years) (P = 0.007). Mutation-negative patients did not develop a third main MEN1 manifestation in the course of follow-up compared to 48.3 % of mutation-positive patients (P < 0.001). Median survival in mutation-positive patients was estimated at 73.0 years (95 % CI, 69.5–76.5) compared to 87.0 years (95 % CI not available) in mutation-negative patients (P = 0.001).ConclusionsMutation-positive and mutation-negative MEN1 patients have a different phenotype and clinical course. Mutation-negative patients develop MEN1 manifestations at higher age and have a life expectancy comparable with the general population. The apparent differences in clinical course suggest that MEN1 mutation-negative patients do not have true MEN1, but another MEN1-like syndrome or sporadic co-incidence of two neuro-endocrine tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0708-1) contains supplementary material, which is available to authorized users.