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 fo...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.展开更多
基金supported by scholarships for A.N.D.from the Medical Faculty,Leipzig University,and for L.L.from the Jürgen Manchot Foundation,and grants from the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)through CRC1423/2(project number 421152132,C04(S.P.,T.S.))CRC1052/3(project number 209933838,B06(T.S.)),B10(D.L.D.))FOR 2149(project number 246212759,P02(S.P.)and P04(T.S.)).
文摘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.
