Volume 9 Issue 5, May 2024:
Article
Dysfunction of the adhesion G protein-coupled receptor latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity
André Nguyen Dietzsch,Hadi Al-Hasani,Joachim Altschmied,Katharina Bottermann,Jana Brendler,Judith Haendeler
ORCID: orcid.org/0000-0001-8507-4540,Susanne Horn,Isabell Kaczmarek,Antje Körner,Kerstin Krause
ORCID: orcid.org/0000-0003-1766-3698,Kathrin Landgraf
ORCID: orcid.org/0000-0002-6878-6033,Diana Le Duc,Laura Lehmann,Stefan Lehr,Stephanie Pick
ORCID: orcid.org/0009-0005-1325-0812,Albert Ricken,Rene Schnorr,Angela Schulz,Martina Strnadová,Akhil Velluva,Heba Zabri,Torsten Schöneberg,Doreen Thor
ORCID: orcid.org/0000-0002-9522-5098 &…Simone Prömel
ORCID: orcid.org/0000-0001-7800-7323
Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide prevalence. Understanding the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity. G protein-coupled receptors (GPCRs) are among the main modulators of metabolism and energy balance. They, for instance, regulate appetite and satiety in certain hypothalamic neurons, as well as glucose and lipid metabolism and hormone secretion from adipocytes. Mutations in some GPCRs, such as the melanocortin receptor type 4 (MC4R), have been associated with early-onset obesity. Here, we identified the adhesion GPCR latrophilin 1 (ADGRL1/LPHN1) as a member of the regulating network governing food intake and the maintenance of energy balance. Deficiency of the highly conserved receptor in mice results in increased food consumption and severe obesity, accompanied by dysregulation of glucose homeostasis. Consistently, we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from obesity. Therefore, we propose that LPHN1 dysfunction is a risk factor for obesity development.
