CHICAGO, Aug. 25 (Xinhua) -- Researchers at the University of Michigan (UM) and Vanderbilt University have identified the function of a protein called the melanocortin 3 receptor (MC3R) that maintains "energy rheostasis".
Like a rheostat on the wall, when the body experiences some sort of metabolic stress that shifts energy levels, fasting or eating a high-fat diet, MC3R ensures that the balance of energy and fat in the body does not drift too far in either direction.
This role in rheostasis makes MC3R a promising new drug target for treating obesity.
"When we eat less and exercise more to lose weight, our bodies sense when the energy balance has tipped below the established lower boundary and try to adjust by using less energy and increasing appetite to return to homeostasis. This lower boundary is what makes it difficult to keep weight off," said lead study author Masoud Ghamari-Langroudi of the Vanderbilt University School of Medicine.
"A drug that targets MC3R has the potential to work as a diet aid, by reducing the rigidity of that lower boundary," said Roger Cone, director of UM Life Sciences Institute.
The protein also plays a role in regulating changes in the body's energy balance that occur as part of the normal life cycle.
Before then, the researchers have discovered that mice lacking the MC3R protein gain less weight than they should during pregnancy, and gain more weight than normal mice during a mouse model of menopause.
The researchers discovered both MC3R and MC4R in mouse brains in the mid-1990s, and then fairly quickly determined MC4R's role in maintaining the setpoint for energy homeostasis: a lack of MC4R is known to be the most common cause of syndromic obesity in humans. But they did not understand why the MC3R protein sometimes led to excessive weight loss and other times to excessive weight gain.
"Now, we finally have an answer," Cone said.