Hyperphagia among patients with Bardet‐Biedl syndrome

Abstract

Summary Background The importance of hyperphagia as a cause for energy imbalance in humans with Bardet-Biedl syndrome (BBS) has not been established. We therefore compared hyperphagic symptoms in patients with BBS versus controls. Methods We studied 13 patients with BBS and 23 nonsyndromic controls with similar age, sex, and BMI z-score. A 13-item hyperphagia questionnaire was completed by patients’ parents/guardians. Results Total hyperphagia questionnaire score was higher in BBS than controls (27.6±9.0 vs. 19.1±7.9, p=0.005). Behavior and drive sub-scales were higher for BBS than controls (12.5±4.1 vs. 7.8±3.2, p=0.001, and 11.2±4.1 vs. 8.3±3.8, p=0.04, respectively); severity was not significantly different between groups (3.8±1.5 vs. 3.0±1.3, p=0.072). After adjustment for demographic variables and BMI-Z score, total and behavior subscale scores remained significantly different between groups, suggesting food-seeking activity, rather than preoccupation with food may be the main hyperphagic feature among patients with BBS. Conclusion Appetite dysregulation may contribute to obesity in BBS.

The role of Rpgrip1l, a component of the primary cilium, in adipocyte development and function

“…Some ciliopathies-that is, Bardet-Biedl syndrome (BBS) and Alström syndrome-also present with comorbid severe obesity (18,19). Hyperphagia, presumably of hypothalamic origin, is a primary contributor to the obesity observed in individuals with ciliopathies (53,54). We have demonstrated that the congenital absence of Rpgrip1l causes decreased leptin sensitivity as a result of impaired leptin receptor trafficking in relation to the primary cilium (16,20).…”

Primary cilia in pancreatic development and disease

“…Disruption of glucose homeostasis in ciliopathies has been discussed primarily in the context of the subgroup of dis-eases characterized by highly penetrant obesity, which include Bardet-Biedl syndrome (BBS) and Alstrom syndrome. A majority of BBS and Alstrom patients are obese, potentially as a result of centrally mediated hyperphagia (Arsov et al, 2006;Lee et al, 2009;Sherafat-Kazemzadeh et al, 2013), and display complications associated with obesity including hypertension, hyperlipidemia, and hyperleptinemia (Beales et al, 1999;Grace et al, 2003;Feuillan et al, 2011;Girard and Petrovsky, 2011). Despite the similarities between the two disorders, the rate of early onset of diabetes is significantly higher in Alstrom patients (Marshall et al, 2005;Marshall et al, 2007;Girard and Petrovsky, 2011) when compared to most cohorts of BBS patients (Beales et al, 1999;Grace et al, 2003;Feuillan et al, 2011), as well as to rates of diabetes in common obesity (Mokdad et al, 2003;Finkelstein, 2008;Bettini et al, 2012).…”

Ciliary disturbances in syndromal and non-syndromal obesity

“…The pathogenesis of obesity in these ciliopathy disorders is however not entirely clear; it seems to be multifactorial in origin. Mouse models suggest a disturbed appetite regulation, abnormalities in body fat composition and a decreased energy expenditure [20][21][22].…”

“…One of the proposed disease mechanisms is disturbance of the central appetite regulation leading to hyperphagia and subsequently obesity. Although in ALMS patients the evidence is not conclusive, BBS patients have indeed shown to suffer from hyperphagia [15,22]. Figure 1 shows a simplified schedule of the neuroendocrine regulation of energy balance.…”