Against the backdrop of the growing epidemic¹ of obesity² in the United States, scientists from the Florida campus of The Scripps Research Institute have made an important new discovery regarding a specific gene³ that plays an important role in keeping a steady balance between our food intake⁴ and energy expenditure⁵. The study may help scientists better understand the keys to fighting obesity and related disorders⁶ such as diabetes⁷. The study, which was published in the November 25, 2011 print edition of The Journal of Biological Chemistry, focused on the melanocortin-3 receptor (MC3R), which normally responds to signals of nutrient⁸ intake.

"What we discovered was quite a surprise," said Scripps Research Associate Professor Andrew Butler, who led the study. "We thought that the actions of the receptor expressed in the brain would be critical for metabolic⁹（新陈代谢的） homeostasis（体内平衡） . However, what we found is that actions of the receptor expressed outside the brain appear to be equally important."

The existence of drug targets in areas outside of the central nervous system (the body's "periphery¹⁰") might help in the effort to develop drugs that influence metabolism¹¹ without major side effects, Butler said.

The findings were made possible by the team's development of a new transgenic（转基因的） animal model, where expression of the MC3R gene can be selectively "switched on" in different cell types.

In the study, the suppression of MC3R expression in the brain and peripheral¹²（外围的） tissues had a marked impact on metabolic homeostasis (equilibrium). Interestingly, mice expressing the MC3R gene in the brain only displayed an obese¹³ phenotype (physical appearance) similar to those where all types of expression was suppressed, indicating that actions of this receptor in the brain are not sufficient to protect against weight gain. The finding that loss of MC3R activity in the periphery impairs¹⁴ metabolic homeostasis is startling, Butler said, and point to a distinct role for MC3R signaling in the peripheral tissues. However, how the actions of these receptors impacts on obesity remains¹⁵ to be determined¹⁶.

"It's clear that these peripheral receptors are important and the new mouse model will let us explore that potential," Butler said.

The study was supported by National Institutes of Health and the Pennington Biomedical Research Foundation.