Anesthetic drugs modulate feeding behavior and hypothalamic expression of the POMC polypeptide precursor and the NPY neuropeptide

Abstract

BackgroundSeveral hypnotic drugs have been previously identified as modulators of food intake, but exact mechanisms remain unknown. Feeding behavior implicates several neuronal populations in the hypothalamic arcuate nucleus including orexigenic neuropeptide Y and anorexigenic pro-opiomelanocortin producing neurons. The aim of this study was to investigate in mice the impact of different hypnotic drugs on food consumption and neuropeptide Y or pro-opiomelanocortine mRNA expression level in the hypothalamic arcuate nucleus.MethodsSaline control, isoflurane, thiopental, midazolam or propofol were administered to C57Bl/6 mice. Feeding behavior was evaluated during 6 h. In situ hybridization of neuropeptide Y and pro-opiomelanocortine mRNAs in the hypothalamus brain region was also performed. Data were analyzed by Kruskal Wallis test and analysis of variance (p < 0.05).ResultsMidazolam, thiopental and propofol induced feeding behavior. Midazolam and thiopental increased neuropeptide Y mRNA level (respectively by 106 and 125%, p < 0.001) compared with control. Propofol and midazolam decreased pro-opiomelanocortine mRNA level by 31% (p < 0,01) compared with control. Isoflurane increased pro-opiomelanocortine mRNA level by 40% compared with control.ConclusionIn our murine model, most hypnotics induced food consumption. The hypnotic-induced regulation of neuropeptide Y and pro-opiomelanocortine hypothalamic peptides is associated with this finding. Our data suggest that administration of some hypnotic drugs may affect hypothalamic peptide precursor and neuropeptide expression and concomittantly modulate food intake. Thus, this questions the choice of anesthetics for better care management of patients undergoing major surgery or at risk of undernutrition.Electronic supplementary materialThe online version of this article (10.1186/s12871-018-0557-x) contains supplementary material, which is available to authorized users.

Postoperative hunger after outpatient surgery in patients anesthetized with propofol vs sevoflurane: a randomized-controlled trial

“…8 The results of our study conflict with other findings suggesting that unlike volatile anesthetics, propofol exerts orexigenic properties. [9][10][11][12] In part, this may be explained by the different populations that have been studied as well as the type and duration of surgery.…”

“…11,12 A potentially confounding variable was the difference in duration of anesthesia between groups: patients in the sevoflurane group had a somewhat longer duration of anesthesia including a higher cumulative dose of remifentanil, which could have impacted feeding behaviour. As sevoflurane is expected to reduce the sensation of hunger, 9,10 we anticipate that this difference in anesthesia time would have (if anything) exaggerated any pro-feeding influence of propofol. Another potentially confounding variable is the effect of other drugs administrated to both groups, including paracetamol, hydroxyzine, dexamethasone, droperidol, and remifentanil.…”

“…For example, we previously reported that, unlike isoflurane, propofol induces feeding behaviour in mice for at least six hours. 9 In clinical studies, compared with isoflurane or halothane, propofol has been reported to enhance a return of the patient's appetite after neurosurgery 10 and ophthalmological procedures. 11 While it has been claimed that propofol is associated with an intense feeling of hunger in outpatients undergoing colonoscopy, no corroborating data were provided.…”

The morphometrical and immunohistochemical investigation of the effect of topiramate on liver and the role of neuropeptide Y receptor in an obese female rat

“…Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide secreted from neurons in the arcuate nucleus of the hypothalamus. NPY also is a main member of hypothalamic neuropeptide signalling systems that contributes to the regulation of food consumption and energy (16). Expression of NPY may be affected by extrinsic agents.…”

The use of midazolam as an appetite stimulant and anxiolytic in the common marmoset (Callithrix jacchus)

“…19,20 They are commonly used for their sedative, anxiolytic, and hypnotic properties, but have also been shown to act as an appetite stimulant in multiple species, including rodents, goats, cats, rhesus macaques, baboons, and humans. [21][22][23][24][25][26][27][28] In marmosets, the benzodiazepine diazepam has been shown to reduce anxiety-like behaviors when exposed to either an open-field test or a predatory confrontation model 29,30 ; however, there are no data supporting the use of any BZ as an appetite stimulant in marmosets, nor is there any evidence that BZs can overcome anxiety-induced inappetence in this species. Given this information, we sought to evaluate the use of the non-selective benzodiazepine midazolam as an appetite stimulant and anxiolytic in the common marmoset.…”