The Melanocortin-4 Receptor Integrates Circadian Light Cues and Metabolism
Deanna M. Arble,Jenna Holland,Nickki Ottaway,Joyce Sorrell,Joshua W. Pressler,Rachel Morano,Rachel Morano,Stephen C. Woods,Stephen C. Woods,Randy J. Seeley,Randy J. Seeley,James P. Herman,James P. Herman,Darleen A. Sandoval,Darleen A. Sandoval,Diego Perez-Tilve +15 more
TLDR
It is suggested 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.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.read more
Citations
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Journal ArticleDOI
Melanocortin-4 receptor-regulated energy homeostasis.
TL;DR: Drawing on recent advances in neuroscience and genetic technologies, the structure and function of the melanocortin-4 receptor circuitry and its role in energy homeostasis are considered.
Journal ArticleDOI
Objectively Measured Light Exposure in Emmetropic and Myopic Adults
TL;DR: Objective devices such as the Actiwatch can be valuable in studies where quantification of environmental factors is critical and various environmental and seasonal measurements revealed significantly different available light in winter versus summer and indoors versus outdoors.
Book ChapterDOI
Central Circadian Clock Regulates Energy Metabolism.
TL;DR: The experimental and observational evidence that suggests a critical role of the central circadian clock in shaping systemic energy metabolism is described and the involvement of endocrine factors, neuropeptides, and the autonomic nervous system in the metabolic functions of thecentral circadian clock is discussed.
Journal ArticleDOI
Deficient melanocortin-4 receptor causes abnormal reproductive neuroendocrine profile in female mice.
Xiao-Lin Chen,Lili Huang,H. Y. Tan,Hongzhuo Li,Ying Wan,Michael A. Cowley,Johannes D. Veldhuis,Chen Chen +7 more
TL;DR: The characteristics of hormone profiles in obese MC4R KO mice indicate thatMC4R plays an important role in regulating LH release, ovulation and reproductive ability probably via hyperphagia-induced obesity.
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STN-PPTg circuits and REM sleep dysfunction in drug-refractory epilepsy.
TL;DR: The study of REM behavior disorder in patients with epilepsy provides unique opportunities to develop new approaches for controlling and preventing refractory epilepsy which does not respond to current pharmacological intervention.
References
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Akira Kohsaka,Aaron D. Laposky,Kathryn Moynihan Ramsey,Kathryn Moynihan Ramsey,Carmela Estrada,Corinne E. Joshu,Yumiko Kobayashi,Fred W. Turek,Joseph Bass +8 more
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Journal ArticleDOI
Divergence of Melanocortin Pathways in the Control of Food Intake and Energy Expenditure
Nina Balthasar,Louise Torp Dalgaard,Charlotte E. Lee,Jia Yu,Hisayuki Funahashi,Todd D. Williams,Manuel A. R. Ferreira,Vinsee Tang,Robert A. McGovern,Christopher D. Kenny,Lauryn M. Christiansen,Elizabeth Edelstein,Brian Choi,Olivier Boss,Carl J. Aschkenasi,Chen-Yu Zhang,Kathleen G. Mountjoy,Toshiro Kishi,Toshiro Kishi,Joel K. Elmquist,Bradford B. Lowell +20 more
TL;DR: It is demonstrated thatMC4Rs in the PVH and/or the amygdala control food intake but that MC4Rs elsewhere control energy expenditure, and association of food intake and energy expenditure reveals unexpected divergence in melanocortin pathways controlling energy balance.
Journal ArticleDOI
Circadian Timing of Food Intake Contributes to Weight Gain
TL;DR: Evidence is provided that nocturnal mice fed a high‐fat diet only during the 12‐h light phase gain significantly more weight than mice fed onlyDuring the 12-h dark phase.
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