Children with Bardet-Biedl syndrome have elevated ghrelin and leptin levels but appear resistant to appetite-suppressing signals, helping explain why obesity is a hallmark of this rare genetic disorder.
Leptin resistanceBBS patients had significantly elevated leptin yet still experienced constant hunger, indicating their brains couldn't respond to the fullness signal
What the researchers found
BBS patients had significantly higher BMI than controls. Plasma levels of acylated ghrelin, total ghrelin, and obestatin were slightly elevated compared to controls, as was the acyl-to-total ghrelin ratio. Most notably, leptin levels were significantly elevated in BBS patients.
Normally, high leptin levels signal the brain to reduce appetite, and ghrelin should decrease after eating. In BBS patients, these negative feedback mechanisms appeared broken — ghrelin remained elevated despite adequate nutrition, and the body appeared resistant to leptin's appetite-suppressing effects. This shifts the hormonal balance toward constant hunger signaling.
Why it matters
Understanding why children with BBS develop severe obesity is critical for developing targeted treatments. This study provides evidence that the obesity isn't simply from overeating — it's driven by measurable hormonal imbalances in peptide signaling. This shifts the conversation from behavioral to biological and opens the door for potential peptide-based interventions like leptin sensitizers or ghrelin modulators.
How the study worked
The researchers measured five appetite-related hormones (total ghrelin, acylated ghrelin, obestatin, leptin, and adiponectin) in blood samples from eight children with BBS. Results were compared to healthy controls and analyzed in relation to body mass index and height. This was a case-control study design.
What this study cannot tell us
The study included only 8 children with BBS, which is a very small sample size even for a rare disease. The cross-sectional design captures hormone levels at one point in time, not how they change over the course of disease. The study measured circulating hormone levels but did not directly assess receptor sensitivity or brain responses to these hormones.
How to read the evidence
This is a small case-control study with only 8 BBS patients. While it provides valuable mechanistic insights about hormonal disruption, the small sample limits generalizability and statistical power.
When this study was published
Published in 2012, this study predates the approval of setmelanotide (2020) for BBS-related obesity. The hormonal findings remain valid and helped build the scientific case for melanocortin pathway-targeted therapies.
The bigger picture
Bardet-Biedl syndrome is one of several rare genetic obesity syndromes (alongside Prader-Willi and MC4R deficiency) that have illuminated how peptide hormones control body weight. The discovery of leptin resistance in BBS contributed to broader understanding of why some people's bodies ignore fullness signals — a mechanism now recognized as relevant to common obesity as well. This research helped pave the way for drugs like setmelanotide, which targets the melanocortin pathway downstream of leptin.
Questions still open
- Could leptin-sensitizing drugs help restore appetite regulation in BBS patients?
- Do the specific BBS gene mutations correlate with the degree of hormonal disruption?
- Would ghrelin receptor antagonists reduce hunger drive in BBS patients?
Common questions
What is Bardet-Biedl syndrome?
Why can't children with BBS simply eat less to control their weight?
Read the original research
Obesity in patients with Bardet-Biedl syndrome: influence of appetite-regulating hormones.
Pediatric nephrology (Berlin, Germany), 27(11), 2065-2071
Citation
Büscher, Anja K; Cetiner, Metin; Büscher, Rainer; Wingen, Anne-Margret; Hauffa, Berthold P; Hoyer, Peter F. (2012). Obesity in patients with Bardet-Biedl syndrome: influence of appetite-regulating hormones.. Pediatric nephrology (Berlin, Germany), 27(11), 2065-2071. https://doi.org/10.1007/s00467-012-2220-y