期刊
ENDOCRINOLOGY
卷 156, 期 5, 页码 1685-1691出版社
ENDOCRINE SOC
DOI: 10.1210/en.2014-1937
关键词
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资金
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases [F32 DK097867-01, R01 DK093848-01, R01 DK082480-01, R01 DK077975]
- Ethicon Endo-Surgery
- Ablaris Therapeutics, Inc
- Novo Nordisk
- Novartis
- Angiochem
- Eisai
- Forest Pharmaceuticals
- Givaudan
- Zealand Pharmaceuticals
- Boehringer Ingelheim International
- Calibrium Ltd.
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.
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