The Melanocortin Pathway: Effects of Voluntary Exercise on the Melanocortin‐4 Receptor Knockout Mice and ACTH(1–24) Ligand Structure Activity Relationships at the Melanocortin‐2 Receptor

Abstract

The melanocortin pathway consists of endogenous agonists, antagonists, G‐protein coupled receptors, and ancillary proteins that mediate the function of the endogenous antagonists. The melanocortin‐4 receptor (MC4R) is involved in the regulation of obesity and the melanocortin‐2 receptor (MC2R) is involved in the regulation of steroidogenesis. Herein, we present the effects of voluntary exercise on the MC4R knockout mice in terms of bypassing the morbid obesity and hyperphagia phenotypes associated with this genetic obesity model. Additionally, a systematic truncation study of the adrenocorticotropin hormone (ACTH 1–24) has been performed and characterized at the cloned MC2R.

• Adrenocorticotropin
• Melanotropin
• Obesity
• MC2R
• Exercise

Acknowledgments

We thank the financial support of NIH grants DK57080, DK64250, and DK63974. A. Todorovic and B. Irani are the recipients of American Heart Association Predoctoral Fellowships. The MC4RKO mice were graciously provided by Millennium Pharmaceuticals. We would also like to thank Bernard Schimmer for his gift of the MC2R stable cell lines.