The melanocortin-4 receptor integrates circadian light cues and metabolism

Endocrinology
Deanna M ArbleDiego Perez-Tilve

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 sug...Continue Reading

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Citations

Jan 28, 2016·Nature Neuroscience·Michael J KrashesAlastair S Garfield
Aug 28, 2015·Epilepsy & Behavior : E&B·Ai-Jun XuHong-Bing Xiang
Nov 5, 2016·Optometry and Vision Science : Official Publication of the American Academy of Optometry·Lisa A Ostrin
Dec 23, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Xiaolin ChenChen Chen
Aug 14, 2020·Physiology & Behavior·Joyce SorrellDiego Perez-Tilve

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