Metabolism-boosting peptide may unlock target for anti-obesity drugs
A new connection between the fat-blocking hormone leptin and a potent metabolism-boosting peptide, aMSH, may lead to a novel target for obesity drugs, according to research published in the online early edition of the Proceedings of the National Academy of Sciences.
The research, conducted at Beth Israel Deaconess Medical Center and Harvard Medical School in collaboration with Brown Medical School and Rhode Island Hospital, showed an active form of aMSH is increased in the brain of mice and rats injected with leptin. Active aMSH stimulates a signaling cascade that decreases appetite and causes the body to increase energy expenditure.
"When you have more of the active peptide [aMSH], the peptide will increase calorie expenditure by acting on specific neuronal cells, so the more peptide you have the more anorexigenic effects you have," says Eduardo Nillni, one of the co-authors of the study and senior investigator in the Division of Endocrinology at Rhode Island Hospital.
The process through which leptin increases levels of the active aMSH peptide in the body remains unknown. Christian Bjørbæk at Beth Israel Deaconess Medical Center is currently working to identify the enzyme that causes aMSH activation. This unknown enzyme, the researcher said, could be a target for anti-obesity drugs.
"If one can activate this enzyme in the brain," notes Christian Bjørbæk, the corresponding author of the study, "it should lead to higher levels of the acetylated form of the peptide and therefore, inhibition of appetite and lower body weight."
"If somehow, through a drug, you can increase activity of aMSH, you’d force the body to burn more calories and lose weight," Nillni says. "That would help so many people."
According to the federal Centers for Disease Control and Prevention, 61 percent of adults are overweight or obese and 13 percent of children and adolescents are seriously overweight. The epidemic is responsible for 300,000 deaths a year and carries an economic toll of $117 billion.
The Beth Israel Deaconess Medical Center / Harvard research team included Bjorbaek, Li Guo and Heike Munzberg. Nillni and Ronald Stuart worked on the project through the Brown/Rhode Island Hospital.
Proceedings of the National Academy of Sciences – www.pnas.org
The Bjorbaek Lab - http://www.monettepunzalan.com/Endocrine/research/labs/bjorbaek/index.asp
Eduardo Nillni - http://bms.brown.edu/faculty/n/enillni/