Science of Self-Preservation How Melanocortin Action in the Brain Modulates Body Weight, Blood Pressure, and Ischemic Damage

The diverse roles of the melanocortin system can be viewed as crucial components of the body's defense mechanisms, whether by limiting ultraviolet light damage to the skin, fueling the drive to eat when energy stores are low, or fine-tuning the inflammatory response to physical trauma to minimize tissue damage. Our knowledge of melanocortin biology continues to evolve and develop. The importance of key parts of the system in the control of energy homeostasis remains unchallenged, with, for example, common variants near MC4-R now being implicated in influencing fat mass, weight, and obesity risk at the population level.69 Furthermore, although not discussed in this review, there is an increasing body of work highlighting the role that increased melanocortin activity has in the pathogenesis of cachexia (see review by Marks et al70). With this ongoing expansion of knowledge, it is surely only a matter of time before pharmaceutical agents derived from these simple peptides come of age. However, whichever niche these drugs eventually occupy, clinicians need to remain mindful of this evolving sphere of influence and remain attuned to potential effects, good and bad, in tissue and organs distant from the primary target. © 2009 American Heart Association, Inc.