TY - JOUR
T1 - Circadian mechanisms in bioenergetics and cell metabolism
AU - Bass, Joseph
N1 - Funding Information:
P01AG011412 (National Institute on Aging NIA), R01DK090625 (NIDDK National Institute of Diabetes and Digestive and Kidney Disease), R01DK100814 (NIDDK National Institute of Diabetes and Digestive and Kidney Disease) 17-2013-511 (Juvenile Diabetes Research Foundation with Helmsley Charitable Trust) 1-INO-2014-178-A-V (Juvenile Diabetes Research Foundation with Helmsley Charitable Trust). I thank the lab members who participated in our cited research and to KM Ramsey for helpful comments and suggestions on the manuscript.
Publisher Copyright:
© The Author(s) 2016.
PY - 2016
Y1 - 2016
N2 - Circadian clocks are biologic oscillators present in all photosensitive species that produce 24-h cycles in the transcription of rate-limiting metabolic enzymes in anticipation of the light-dark cycle. In mammals, the clock drives energetic cycles to maintain physiologic constancy during the daily switch in behavioral (sleep/wake) and nutritional (fasting/feeding) states. A molecular connection between circadian clocks and tissue metabolism was first established with the discovery that 24-h transcriptional rhythms are cell-autonomous and selfsustained in cultured fibroblasts, and that clocks are present in most tissues and comprise a robust temporal network throughout the body. A central question remains: how do circadian transcriptional programs integrate physiologic systems within individual cells of the intact animal and how does the ensemble of local clocks align temporal harmonics in the organism with the environment? Our approach to studies of metabolic regulation by the molecular clock began with analyses of metabolic pathologies in circadian mutant animals, experiments that first became possible with the cloning of the clock genes in the late 1990s. A paradox in our early studies was that the effects of circadian clock disruption were both nutrient-and time-dependent, so that, under fed conditions, animals exhibited diabetes whereas during fasting, they decompensated and died. Application of a broad range of tissue-specific genetic and biochemical approaches has now begun to provide mechanistic insight into the circadian control of metabolism.
AB - Circadian clocks are biologic oscillators present in all photosensitive species that produce 24-h cycles in the transcription of rate-limiting metabolic enzymes in anticipation of the light-dark cycle. In mammals, the clock drives energetic cycles to maintain physiologic constancy during the daily switch in behavioral (sleep/wake) and nutritional (fasting/feeding) states. A molecular connection between circadian clocks and tissue metabolism was first established with the discovery that 24-h transcriptional rhythms are cell-autonomous and selfsustained in cultured fibroblasts, and that clocks are present in most tissues and comprise a robust temporal network throughout the body. A central question remains: how do circadian transcriptional programs integrate physiologic systems within individual cells of the intact animal and how does the ensemble of local clocks align temporal harmonics in the organism with the environment? Our approach to studies of metabolic regulation by the molecular clock began with analyses of metabolic pathologies in circadian mutant animals, experiments that first became possible with the cloning of the clock genes in the late 1990s. A paradox in our early studies was that the effects of circadian clock disruption were both nutrient-and time-dependent, so that, under fed conditions, animals exhibited diabetes whereas during fasting, they decompensated and died. Application of a broad range of tissue-specific genetic and biochemical approaches has now begun to provide mechanistic insight into the circadian control of metabolism.
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U2 - 10.1007/978-3-319-27069-2_3
DO - 10.1007/978-3-319-27069-2_3
M3 - Article
AN - SCOPUS:85006757139
SN - 1861-2253
VL - 0
SP - 25
EP - 32
JO - Research and Perspectives in Endocrine Interactions
JF - Research and Perspectives in Endocrine Interactions
ER -