Document Type
Article
Language
eng
Publication Date
5-1-2015
Publisher
Endocrine Society
Source Publication
Endocrinology
Source ISSN
0013-7227
Abstract
The melanocortin system directs diverse physiological functions from coat color to body weight homoeostasis. A commonality among melanocortin-mediated processes is that many animals modulate similar processes on a circannual basis in response to longer, summer days, suggesting an underlying link between circadian biology and the melanocortin system. Despite key neuroanatomical substrates shared by both circadian and melanocortin-signaling pathways, little is known about the relationship between the two. Here we identify a link between circadian disruption and the control of glucose homeostasis mediated through the melanocortin-4 receptor (Mc4r). Mc4r-deficient mice exhibit exaggerated circadian fluctuations in baseline blood glucose and glucose tolerance. Interestingly, exposure to lighting conditions that disrupt circadian rhythms improve their glucose tolerance. This improvement occurs through an increase in glucose clearance by skeletal muscle and is food intake and body weight independent. Restoring Mc4r expression to the paraventricular nucleus prevents the improvement in glucose tolerance, supporting a role for the paraventricular nucleus in the integration of circadian light cues and metabolism. Altogether these data suggest that Mc4r signaling plays a protective role in minimizing glucose fluctuations due to circadian rhythms and environmental light cues and demonstrate a previously undiscovered connection between circadian biology and glucose metabolism mediated through the melanocortin system.
Recommended Citation
Arble, Deanna M.; Holland, Jenna; Ottaway, Nickki; Sorrell, Joyce; Pressler, Joshua W.; Morano, Rachel; Woods, Stephen C.; Seeley, Randy J.; Herman, James P.; Sandoval, Darleen A.; and Perez-Tilve, Diego, "The Melanocortin-4 Receptor Integrates Circadian Light Cues and Metabolism" (2015). Biological Sciences Faculty Research and Publications. 653.
https://epublications.marquette.edu/bio_fac/653
Comments
Accepted version. Endocrinology, Vol. 156, No. 5, (May1, 2015): 1685–1691, DOI.© 2015 Oxford University Press. Used with permission.
Deanna M. Arble was affiliated with the University of Cincinnati at the time of publication.