The findings implicate the hormone in the maintenance of normal body weight and suggest that drugs that mimic the chemical might offer a new avenue for obesity treatment, report the studies' lead authors Stephen O'Rahilly, of the Cambridge Institute for Medical Research in the United Kingdom, and Heiko Krude, of Charit Universittsmedizin Berlin in Germany.
The hormone's important role in maintaining body weight had been overlooked primarily because mice and rats, the subjects of much obesity research, do not produce the chemical, they added. Earlier studies had focused their attention almost entirely on the related chemical α-MSH, a hormone derived from the same precursor protein that is known to suppress appetite in humans and rodents.
"The assumption had been that α-MSH was most important at keeping energy balanced in people," O'Rahilly said. "The new studies point the finger at the neglected sibling, -MSH."
Both α-MSH and -MSH are derived from a protein complex known as proopiomelanocortin (POMC). The POMC protein is produced by neurons that play a central role in weight regulation in the brain. Earlier studies had demonstrated that loss of POMC leads to severe obesity, a phenomenon that researchers had assumed resulted from the loss of α-MSH.
In order to determine whether mutations within the melanocortin hormones might predispose people to obesity, O'Rahilly's group screened the protein-coding regions of the POMC gene in 538 Caucasian children from the U.K. with severe early-onset obesity. The group found an abnormal variant of -MSH in five of the children studied.
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Contact: Heidi Hardman
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Cell Press
7-Feb-2006