A higher response of plasma neuropeptide Y, growth hormone, leptin levels and extracellular glycerol levels in subcutaneous abdominal adipose tissue to Acipimox during exercise in patients with bulimia nervosa: single-blind, randomized, microdialysis study

Abstract

BackgroundNeuropeptide Y (NPY) is an important central orexigenic hormone predominantly produced by the hypothalamus, and recently found to be secreted in adipose tissue (AT). Acipimox (Aci) inhibits lipolysis in AT and reduces plasma glycerol and free fatty acid (FFA) levels. Exercise and Aci are enhancers of growth hormone (GH) and NPY secretion and exercise may alter leptin levels. We expect to find abnormal neuropeptidergic response in plasma and AT in patients with bulimia nervosa (BN). We hypothesize that Aci influences these peptides via a FFA-independent mechanism and that Aci inhibits lipolysis through a cyclic adenosine monophosphate (cAMP)-dependent pathway. Dysregulations of the AT-brain axis peptides might be involved in binge eating as is the case in BN.MethodsThe objective of this study was to determine the responses of plasma NPY, GH, leptin, FFA and glycerol levels to exercise in BN patients and healthy women (C) given the anti-lipolytic drug Aci or placebo. The secondary objective of this study was to compare the responses of extracellular glycerol levels and plasma glycerol levels to exercise alone or together with Aci administration in BN patients and C women. Extracellular glycerol was measured in vivo in subcutaneous (sc) abdominal AT using microdialysis. Eight BN and eight C women were recruited for this single-blind, randomized study. Aci or placebo was given 1 hour before the exercise (45 min, 2 W/kg of lean body mass [LBM]). NPY, GH, leptin, FFA, glycerol plasma and AT glycerol levels were measured using commercial kits.ResultsThe primary outcome of this study was that the exercise with Aci administration resulted in plasma NPY and GH increase (after a 45-minute exercise) and leptin (after a 90-minute post-exercise recovering phase) increased more in BN patients. The secondary outcomes of this study were that the exercise with Aci administration induced a higher decrease of extracellular glycerol in BN patients compared to the C group, while the exercise induced a higher increase of glycerol concentrations in sc abdominal AT of BN patients. Plasma glycerol levels decreased more in BN patients and plasma FFA levels were depressed in both groups after the exercise with Aci administration. The exercise induced similar increases in plasma NPY, GH, FFA and glycerol levels, and a similar decrease in the plasma leptin level in both groups.ConclusionsWe confirm the results of a single-blind, randomized, microdialysis study, i.e. that the Aci-induced elevation in plasma NPY and GH levels during the exercise is higher in BN patients and that Aci increased plasma leptin levels in the post-exercise recovering phase (90-minute) more in BN patients. The post-exercise rise (45-minute) in AT glycerol is much more attenuated by acute Aci treatment in BN patients. Simultaneously, we found facilitated turnover of plasma glycerol after the exercise together with Aci administration in BN. Our results support the hypotheses that Aci exerts an effect on the FFA-independent and cAMP-dependent mechanism.Trial Re...

The Role of “Mixed” Orexigenic and Anorexigenic Signals and Autoantibodies Reacting with Appetite-Regulating Neuropeptides and Peptides of the Adipose Tissue-Gut-Brain Axis: Relevance to Food Intake and Nutritional Status in Patients with Anorexia Nervosa and Bulimia Nervosa

“…In our previous studies, we observed in vivo increased SNS activity in subcutaneous abdominal AT in AN and BN patients [6, 33–36]. The cause and pathogenesis of AN and BN, however, remain unknown.…”

“…It has been reported that NPY can attenuate specific behavior when the organism is stressed, and antistress effects of NPY are relevant to psychiatric conditions such as AN and BN [6, 155, 156] and that NPY has an anxiolytic and antidepressive behavior profile [157]. Interestingly, it is possible that NPY contributes to both binge eating and subsequent purging in BN because NPY itself has been demonstrated to induce an emetic response [158].…”

“…However, plasma concentrations of NPY in patients with BN were significantly elevated in comparison to controls [6, 11, 13, 14, 161] (Table 1). In our recent study, we revealed that antilipolytic drug Aci during short-term exercise further increases plasma NPY levels in patients with BN [6]. …”

Adipose Tissue as an Endocrine Organ: An Update on Pro-inflammatory and Anti-inflammatory Microenvironment

“…Hypoleptinaemia is actually accompanied by a decrease in basal energy expenditure in women with amenorrhea. Indeed, in anorexia nervosa (AN) and bulimia nervosa (BN) patients, plasma leptin levels were found to be lower than in normal weight controls (Nedvídková et al, 2000;Dostálová et al, 2007;Smitka et al, 2011Smitka et al, , 2013a. However, realimentation leads to an increase in plasma leptin levels in AN and BN patients.…”

The role of adipocytokines on depressive symptoms of patients with chronic kidney disease

“…On the other hand, neuropeptide Y, produced by hypothalamus and adipose tissue, together with ghrelin, produced by stomach and involved in short term regulation of feeding and long term regulation of energy metabolism, are both orexigenic hormones. [4][5][6][7][8][9] In addition to hypothalamic satiety center, receptors for leptin, ghrelin, resistin and neuropeptide Y have been identified in limbic areas of the brain that regulate emotion. 10,11 Among the most prevalent mental illnesses, depression is increasing in the western world and these peptides were reported to play a role in emergence of emotional disturbances like depression.…”