Using Peptides to Trigger Satiety in Individuals with LEPR Mutation
Posted by Leanne Kodsman on
A new study shows that researchers were able to successfully treat obesity in patients whose obesity is caused by a genetic defect. The researcher also provides new information about the mechanics of how the brain receives signals of satiety.
A mutation in the leptin receptor (LEPR) gene can cause extreme hunger, beginning in the first months of life. Affected individuals develop extreme obesity during their childhood years, to the extent that increased exercise and reduced caloric intake are insufficient to stabilize body weight. Not only that, but other obesity treatments - like surgical options - fail to benefit these individuals, which serves to highlight the importance of finding a drug-based treatment approach.
A mutation in the leptin receptor (LEPR) gene can cause extreme hunger, beginning in the first months of life. Affected individuals develop extreme obesity during their childhood years, to the extent that increased exercise and reduced caloric intake are insufficient to stabilize body weight. Not only that, but other obesity treatments - like surgical options - fail to benefit these individuals, which serves to highlight the importance of finding a drug-based treatment approach.
Peptides and MC4R
Within the past couple of years, researchers have demonstrated that treatment using a peptide to activate the melanocortin 4 receptor (MC4R) could play a key role in how the body metabolizes energy and regulates body weight.
Leptin - also commonly referred to as the satiety or starvation hormone - normally binds to LEPR, which sets off a series of actions that lead up to the production of melanocyte-stimulating hormone (MSH). The MSH binds to its receptor (MC4R), sending the body signals indicating satiety/fullness.
For individuals for whom LEPR is defective, this chain of actions is interrupted, which means their body does not recognize when hunger is satisfied.
Activating Signals of Satiety
Researchers used a peptide that binds to MC4R in the brain, finding that this activation triggered the normal signals of fullness. Not only that, but the team was able to record significant weight loss in patients who had the genetic LEPR mutation.
The scientists were able to demonstrate that treatment in this way leads to the activation of a critical signaling pathway, the significance of which has previously been underestimated. Additionally, there were no observed severe side effects (in contract to other preparations with a similar mode of action).
Researchers hope that further research will determine if other patients with dysfunctions affecting the same signaling pathway could also be suitable candidates for this treatment.
Further Reading & References:
Karine Clment, Heike Biebermann, I. Sadaf Farooqi, Lex Van der Ploeg, Barbara Wolters, Christine Poitou, Lia Puder, Fred Fiedorek, Keith Gottesdiener, Gunnar Kleinau, Nicolas Heyder, Patrick Scheerer, Ulrike Blume-Peytavi, Irina Jahnke, Shubh Sharma, Jacek Mokrosinski, Susanna Wiegand, Anne Mller, Katja Wei, Knut Mai, Joachim Spranger, Annette Grters, Oliver Blankenstein, Heiko Krude, Peter Khnen. MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency. Nature Medicine, 2018; DOI: 10.1038/s41591-018-0015-9
Charit - Universittsmedizin Berlin. "Switching off insatiable hunger: A new drug to help young patients with genetic obesity." ScienceDaily. ScienceDaily, 8 May 2018. www.sciencedaily.com/releases/2018/05/180508131029.htm.
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