Appetite- and weight-inducing and -inhibiting neuroendocrine factors in Prader–Willi syndrome, Bardet–Biedl syndrome and craniopharyngioma versus anorexia nervosa

Abstract

Obesity is reaching endemic state and has a major impact on health and economy. In most cases obesity is caused by life style factors. However, the risk of becoming obese differs highly between people. Individual differences in life style, genetic, and neuroendocrine factors play a role in satiety, hunger and regulation of body weight. In a small percentage of children and adults with obesity, an underlying hormonal or genetic cause can be found. The aim of this review is to present and compare data on the extreme ends of the obesity and undernutrition spectrum in patients with Prader-Willi syndrome (PWS), Bardet-Biedl syndrome (BBS), acquired hypothalamic obesity in craniopharyngioma patients, and anorexia nervosa. This may give more insight in the role of neuroendocrine factors and might give direction for future research in conditions of severe obesity and underweight.

Hyperphagia and Impulsivity: Use of self-administered Dykens' and in-house Impulsivity questionnaires to characterize eating behaviors in children with severe and early-onset obesity

“…As the severity dimension of the Dykens' questionnaire explores time spent talking about food and interference with daily life [10], our results highlight the signi cant pre-occupation with food that children with early-onset obesity have, with di cult food control and poor tolerance of food restriction. This preoccupation is consistent with the pathophysiological mechanisms of early-onset obesity previously described [1,4,6]. The lack of signi cant differences across the impulsivity and hyperphagia scores of the HO, IDO and CO groups suggests that disordered eating behavior is a common feature in early onset obesity, even allowing for signi cant difference early in each child's life.…”

“…These results are related to the secondary alterations to the hypothalamic damage that likely induce an earlier obesity picture and continuum of a phenotype already described [1,4,6]. The abnormal development of high BMI with no adiposity rebound seem to be very strong elements indicative of the presence of HO and should be agged in cases of uncontrollable hyperphagia, as described in other situations [24][25][26].…”

“…The melanocortin pathway in the hypothalamus regulates appetite and eating behavior and variations in the genes encoding the melanocortin-4 receptor (MC4R) have been linked to severe obesity in children [2]. Impairment of the hypothalamus function due to any genetic or lesional cause is responsible for global neuroendocrine pathology, named hypothalamic obesity (HO) [1,[3][4][5][6]. HO is rare (< 5% all obesities), and models exist to understand the mechanisms of early-onset HO [1,7].…”

Contribution of Ghrelin to the Pathogenesis of Growth Hormone Deficiency

“…It appears that ghrelin does not actually cause weight gain or loss, but rather is one of the components of the compensatory mechanism of energy homeostasis [74]. It was proved that in obese patients, ghrelin concentrations were reduced [75], while in patients with anorexia nervosa or with malnutrition, they were increased [76][77][78][79][80].…”

Metabolomic profiling of Prader-Willi syndrome compared with essential obesity

“…Though clinical studies with conflicting results have been published, PWS-associated obesity exhibits clinical characteristics that are somewhat different from those of essential obesity (EOB), including body composition (particularly, adipose tissue), neuroendocrine system (e.g., ghrelin, oxytocin, and adiponectin), response to body weight reduction programs, occurrence of obesity-related comorbidities such as type 2 diabetes mellitus (T2DM), and long-term cardiovascular prognosis ( 6 – 12 ).…”