Postprandial hyperglycemia stimulates neuroglial plasticity in hypothalamic POMC neurons after a balanced meal

Mechanistic studies in rodents evidenced synaptic remodeling in neuronal circuits that control food intake. However, the physiological relevance of this process is not well defined. Here, we show that the firing activity of anorexigenic POMC neurons located in the hypothalamus is increased after a standard meal. Postprandial hyperactivity of POMC neurons relies on synaptic plasticity that engages pre-synaptic mechanisms, which does not involve structural remodeling of synapses but retraction of glial coverage. These functional and morphological neuroglial changes are triggered by postprandial hyperglycemia. Chemogenetically induced glial retraction on POMC neurons is sufficient to increase POMC activity and modify meal patterns. These findings indicate that synaptic plasticity within the melanocortin system happens at the timescale of meals and likely contributes to short-term control of food intake. Interestingly, these effects are lost with a high-fat meal, suggesting that neuroglial plasticity of POMC neurons is involved in the satietogenic properties of foods.Contrôle nerveux de la prise alimentaire et du métabolisme par une molécule neurale d'adhésion cellulaireISITE " BFCRéseau d'Innovation sur les Voies de Signalisation en Sciences de la Vi

Hypothalamic control of prolactin release in the rainbow trout,Salmo gairdneri: in vitro studies

Hypothalamic control of prolactin (PRL) release in immature rainbow trout Salmo gairdneri was investigated using an in vitro perifusion system of the rostral pars distalis. Hypothalamic extract of trout induced a dose dependent stimulation of PRL release. A similar effect was observed when infusing the medium from a 24h static incubation of the hypothalamus. Extracts from different control tissues (muscle, liver, gut) did not change in vitro release, thus confirming the specificity of this stimulatory effect. Hypothalamic extract from adult male rat, known to contain PRL release inhibiting factors, stimulated in vitro PRL secretion in rainbow trout. This suggests that PRL cells are predominantly influenced by PRL releasing factors. Measurement of TRH and serotonin content in trout hypothalamus indicated consistent physiological levels of these two factors. HPLC studies of hypothalamic extract showed that immunoreactive - TRH eluted at the same place as labelled TRH standard. Moreover, pizotifen, a serotonin antagonist, partially inhibited the stimulation observed with trout hypothalamic extract. These results suggest that, in immature rainbow trout, PRL release is under stimulatory hypothalamic control and that serotonin and probably TRH play a major role in this control

La ghréline, un exemple saisissant de pléïotropie des peptides neuroendocriniens

Ghrelin, a peptide predominantly produced by the stomach, has been discovered as a natural ligand of the growth hormone secretagogue receptor (GHS-R) type 1a. Shortly there after, it attracted enormous interest since it appeared as the first peripheral orexigenic factor. Besides, ghrelin exerts other neuroendocrine metabolic and non-endocrine actions (e.g. cardiovascular activities) that may rely on the widespread distribution of ghrelin and its receptor (GHS-R). The existence of several GHS-R subtypes and evidences that neuroendocrine and metabolic but not all other ghrelin actions are dependent on acylation on serine 3 add further complexity to the system whose major physiological role remains to be definitely elucidated. Ghrelin knockout(-/-) mice are neither anorectic nor dwarf though GHS-R-/- are slightly underweight and do not respond to ghrelin with increased GH secretion or appetite. Thus, the continuation of the fascinating ghrelin story as well as its potential pathophysiological implications in endocrinology and internal medicine remain open avenues for future investigations

Ghrelin/obestatin ratio in twopopulations with low bodyweight: Constitutional thinness and anorexia nervosa: constitutional thinness and anorexia nervosa

International audienceConstitutional thinness (CT) and anorexia nervosa (AN) are two categories of severely underweight subjects. Some appetite-regulating hormones display opposite levels in AN and CT. While levels of ghrelin, an orexigenic hormone, fit with the normal food intake in CT, the lack of efficacy of increased ghrelin levels in AN is not clear. Obestatin is a recently described peptide derived from the preproghrelin gene, reported to inhibit appetite in contrast to ghrelin. The aim of this study was to determine whether the circadian profile of obestatin, total and acylated ghrelin levels is different in CT subjects when compared with AN patients.Six-points circadian profiles of plasma obestatin, acylated ghrelin, total ghrelin and other hormonal and nutritional parameters were evaluated in four groups of young women: 10 CT, 15 restricting-type AN, 7 restored from AN and 9 control subjects.Obestatin circadian levels were significantly higher in AN (p < 0.0001) while no difference was found between CT and control subjects. Acylated and total ghrelin were found increased in AN. Acylated ghrelin/obestatin and total ghrelin/obestatin were found decreased in AN compared to CT or C subjects (p < 0.05). The percentage of acylated ghrelin was found decreased in CT group (p < 0.05).The decreased ghrelin/obestatin ratio found in AN might participate in the restraint in nutriment intake of these patients. In contrast, in CT a lower percentage of acylated over total ghrelin might be considered in the aetiology of this condition

Mechanisms and predictors of menses resumption once normal weight is reached in anorexia nervosa

Abstract Background In cases of Anorexia Nervosa (AN), achieving weight gain recovery beyond the lower limits set by the World Health Organization and normalizing classical nutritional markers appears to be essential for most patients. However, this is not always adequate to restore menstrual cycles. This discrepancy can cause concern for both patients and healthcare providers, and can impact the medical management of these individuals. Thus, the purpose of this study was to assess the ability of anthropometric and hormonal factors to predict the resumption of menstrual cycles in individuals with anorexia nervosa upon reaching a normal body weight. Method Patients with AN who had achieved a normal Body Mass Index but had not yet resumed their menstrual cycles (referred to as ANRec) were evaluated on two occasions: first at visit 1 and then again 6 months later, provided their body weight remained stable over this period (visit 2). Among the 46 ANRec patients who reached visit 2, they were categorized into two groups: 20 with persistent amenorrhea (PA-ANRec) and 26 who had regained their menstrual cycles (RM-ANRec). Anthropometric measurements, several hormone levels, Luteinizing Hormone (LH) pulsatility over a 4-h period, and LH response to gonadotropin-releasing hormone injection (LH/GnRH) were then compared between the two groups at visit 1. Results Patients in the RM-ANRec group exhibited higher levels of follicular stimulating hormone, estradiol, inhibin B, LH/GnRH, and lower levels of ghrelin compared to those in the PA-ANRec group. Analysis of Receiver Operating Characteristic curves indicated that having ≥ 2 LH pulses over a 4-h period, LH/GnRH levels ≥ 33 IU/l, and inhibin B levels > 63 pg/ml predicted the resumption of menstrual cycles with a high degree of specificity (87%, 100%, and 100%, respectively) and sensitivity (82%, 80%, and 79%, respectively). Conclusions These three hormonal tests, of which two are straightforward to perform, demonstrated a high predictive accuracy for the resumption of menstrual cycles. They could offer valuable support for the management of individuals with AN upon achieving normalized weight. Negative results from these tests could assist clinicians and patients in maintaining their efforts to attain individualized metabolic targets. Trial registration IORG0004981

The role of the small bowel in the regulation of circulating ghrelin levels and food intake in the obese Zucker rat.

International audienceCirculating levels of ghrelin, a stomach peptide that promotes food intake, rise before and fall after meal. We aimed to investigate whether there is an independent contribution of the small bowel to the regulation of ghrelin and appetite. A duodenal-jejunal bypass (DJB) with preservation of normal gastric volume and exposure to nutrients was performed in 12-wk-old obese Zucker ZDF fa/fa rat. Food intake, weight gain, 48-h fasting, and 24-h refeeding levels of total and acylated ghrelin were measured. The DJB was challenged against gastric banding (GB), diet, and a sham operation in matched animals. Normal controls were age-matched Wistar rats, which underwent either DJB or a sham operation. The Zucker obese animals showed a paradoxical increase of acylated ghrelin levels after refeeding (+30% with respect to fasting levels; P = 0.001), an abnormality that was completely reversed only by the DJB (-30%; P = 0.01) but not after GB, diet, or sham operation. In obese rats, the DJB resulted in significantly less food intake and weight gain compared with both GB (P < 0.05) and sham operation (P < 0.01). In sharp contrast, the DJB did not alter food intake and weight gain in normal rats. The DJB does not physically restrict the flow of food but restores meal-induced suppression of acylated ghrelin and significantly reduces food intake in Zucker obese rats. These findings suggest an independent intestinal contribution to the regulation of the dynamic ghrelin response to eating and the possibility that defective signaling from the proximal bowel could be involved in the pathogenesis of obesity/hyperphagia

Absence de prise de poids après 4 semaines de surnutrition lipidique chez les maigreurs constitutionnelles : Profil des hormones de la régulation de l'appétit

supplément 2Introduction. À l'opposé de la résistance à la perte de poids des obèses, les maigreurs constitutionnelles (MC) ont naturellement un indice de masse corporelle (IMC) bas (13 - 17,5 kg/m2) sans trouble du comportement alimentaire, ni anomalie biologique ou hormonale, avec des règles conservées, une balance énergétique stable et un profil hormonal anorexigène en image en miroir de l'obésité. Nous avons voulu tester l'hypothèse d'une résistance à la prise de poids chez les MC. Patients et méthodes. 10 femmes MC (IMC < 17,5 kg/m2) et 10 femmes contrôles (C, IMC : 18,5-23 kg/m2) ont réalisé 4 semaines de surnutrition lipidi que (630kcal), encadrées par 3 bilans (initial, 1 mois et 2 mois) : DXA, PYY, GLP-1, ghréline et obéstatine, au cours d'un repas test, calorimétrie indirecte, génomique sur biopsies musculaire et adipeuse et métabolome urinaire. Résultats. Malgré une surnutrition significative et comparable dans les 2 groupes, la prise de poids n'a été significative que chez les C (+ 1 kg) avec une perte de poids significative chez les MC (- 0,370 kg). La surnutrition a entrainé une augmentation significative du métabolisme basal chez les MC uniquement, sans modification significative chez les C, ni modification de l'activité physique dans les 2 groupes. La surnutrition a entrainé une exacerbation du profil anorexigène chez les MC et un profil orexigène chez les C : PYY significativement augmenté chez les MC mais pas chez les C; temps d'exposition post prandial au GLP-1 significativement augmenté chez les MC mais pas chez les C; ghréline, ghréline octanoylée/totale et ghréline/obéstatine significativement augmentés chez les C mais pas chez les MC. Conclusion. La surnutrition lipidique de 4 semaines n'a pas permis de faire prendre du poids aux MC mais a entrainé une augmentation du MB et l'exacerbation du profil anorexigène des hormones de la régulation de l'appétit