Crosstalk between Components of Circadian and Metabolic Cycles in Mammals

Asher, Gad; Schibler, Ueli

doi:10.1016/j.cmet.2011.01.006

Cited by 551 publications

(512 citation statements)

References 107 publications

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“…We wish to emphasize that circadian clocks do not work in isolation, but in tight cooperation with acute regulatory mechanisms. For example, glucose homeostasis is governed by circadian oscillators in pancreatic b cells (Marcheva et al 2010) and hepatocytes (Lamia et al 2008), hormones of the endocrine pancreas such as insulin and glucagon, glucose-sensitive neurons in the brain stem and the hypothalamus acting through the peripheral nervous system on the endocrine pancreas (Marty et al 2007), glucocorticoid hormones, and allosteric mechanisms depending on metabolite concentration that tunes the activity of the enzymes responsible for glucose storage, catabolism, and anabolism (Asher and Schibler 2011). Likewise, xenobiotic detoxification is tuned by a combination of diurnal regulation of gene expression and substrate-induced responses acting through transcription factors such as constitutive androstane receptor (CAR), pregnane X receptor, peroxisome proliferator-activated receptor a, and arylcarbohydrate/dioxin receptor (for review, see Levi and Schibler 2007).…”

Section: Discussionmentioning

confidence: 99%

The Mammalian Circadian Timing System: Synchronization of Peripheral Clocks

Saini

Suter²,

Liani³

et al. 2011

Cold Spring Harbor Symposia on Quantitative Biology

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Mammalian physiology has to adapt to daily alternating periods during which animals either forage and feed or sleep and fast. The adaptation of physiology to these oscillations is controlled by a circadian timekeeping system, in which a master pacemaker in the suprachiasmatic nucleus (SCN) synchronizes slave clocks in peripheral organs. Because the temporal coordination of metabolism is a major purpose of clocks in many tissues, it is important that metabolic and circadian cycles are tightly coordinated. Recent studies have revealed a multitude of signaling components that possibly link metabolism to circadian gene expression. Owing to this redundancy, the implication of any single signaling pathway in the synchronization of peripheral oscillators cannot be assessed by determining the steady-state phase, but instead requires the monitoring of phase-shifting kinetics at a high temporal resolution.

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Section: Discussionmentioning

confidence: 99%

The Mammalian Circadian Timing System: Synchronization of Peripheral Clocks

Saini

Suter²,

Liani³

et al. 2011

Cold Spring Harbor Symposia on Quantitative Biology

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“…Despite accumulating evidence supporting the role of PPAR β / δ in metabolic control and energy homeostasis [6, 50] and abundant data showing association between metabolism and circadian rhythm [51], little is known concerning the influence of PPAR β / δ in circadian rhythm unlike PPAR α and PPAR γ , even though mRNA level of PPAR β / δ is cyclic in mouse liver and brown adipose tissue [25]. REV-ERB α and miR-122 may serve as a possible link between PPAR β / δ and circadian clock.…”

Section: Pparβ/δ and Circadian Clockmentioning

confidence: 99%

PPARs Integrate the Mammalian Clock and Energy Metabolism

2014

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Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of numerous target genes. PPARs play an essential role in various physiological and pathological processes, especially in energy metabolism. It has long been known that metabolism and circadian clocks are tightly intertwined. However, the mechanism of how they influence each other is not fully understood. Recently, all three PPAR isoforms were found to be rhythmically expressed in given mouse tissues. Among them, PPARα and PPARγ are direct regulators of core clock components, Bmal1 and Rev-erbα, and, conversely, PPARα is also a direct Bmal1 target gene. More importantly, recent studies using knockout mice revealed that all PPARs exert given functions in a circadian manner. These findings demonstrated a novel role of PPARs as regulators in correlating circadian rhythm and metabolism. In this review, we summarize advances in our understanding of PPARs in circadian regulation.

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“…Mounting evidence suggests that circadian clocks orchestrate our daily physiology and metabolism (3)(4)(5)(6). The mammalian circadian timing system consists of a central pacemaker in the brain that is entrained by daily light-dark cycles and synchronizes subsidiary oscillators in virtually all cells of the body, in part by driving rhythmic feeding behavior.…”

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confidence: 99%

Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins

Neufeld-Cohen

Robles

Aviram

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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207

192

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Mitochondria are major suppliers of cellular energy through nutrients oxidation. Little is known about the mechanisms that enable mitochondria to cope with changes in nutrient supply and energy demand that naturally occur throughout the day. To address this question, we applied MS-based quantitative proteomics on isolated mitochondria from mice killed throughout the day and identified extensive oscillations in the mitochondrial proteome. Remarkably, the majority of cycling mitochondrial proteins peaked during the early light phase. We found that rate-limiting mitochondrial enzymes that process lipids and carbohydrates accumulate in a diurnal manner and are dependent on the clock proteins PER1/2. In this conjuncture, we uncovered daily oscillations in mitochondrial respiration that peak during different times of the day in response to different nutrients. Notably, the diurnal regulation of mitochondrial respiration was blunted in mice lacking PER1/2 or on a high-fat diet. We propose that PERIOD proteins optimize mitochondrial metabolism to daily changes in energy supply/demand and thereby, serve as a rheostat for mitochondrial nutrient utilization.M itochondria serve as major suppliers of cellular energy through nutrient oxidation. One of the major challenges that mitochondria face is the adaptation to changes in nutrient supply and energy demand. An inability of mitochondria to deal with altered nutrient environment is associated with metabolic diseases, such as diabetes and obesity (1, 2).Mitochondria oxidize carbohydrates and lipids to generate ATP by a process known as oxidative phosphorylation. Pyruvate and fatty acids are transported from the cytoplasm into the mitochondrial matrix, where they are catabolized into acetyl CoA. Pyruvate is converted to acetyl CoA through the action of the pyruvate dehydrogenase complex (PDC), whereas fatty acids are oxidized through a cycle of reactions that trim two carbons at a time, generating one molecule of acetyl CoA in each cycle [i.e., fatty acid oxidation (FAO)]. The acetyl groups are then fed into the Krebs cycle for additional degradation, and the process culminates with the transfer of acetyl-derived high-energy electrons along the respiratory chain.Mounting evidence suggests that circadian clocks orchestrate our daily physiology and metabolism (3-6). The mammalian circadian timing system consists of a central pacemaker in the brain that is entrained by daily light-dark cycles and synchronizes subsidiary oscillators in virtually all cells of the body, in part by driving rhythmic feeding behavior. The core clock molecular circuitry relies on interlocked transcription-translation feedback loops that generate daily oscillations of gene expression in cultured cells and living animals (7). Many transcriptomes (8-12) and more recently, several proteomics (13-15) and metabolomics studies (16-21) highlighted the pervasive circadian control of metabolism.Rest-activity and feeding-fasting cycles that naturally occur throughout the day impose pronounced changes in nutrient s...

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Crosstalk between Components of Circadian and Metabolic Cycles in Mammals

Cited by 551 publications

References 107 publications

The Mammalian Circadian Timing System: Synchronization of Peripheral Clocks

The Mammalian Circadian Timing System: Synchronization of Peripheral Clocks

PPARs Integrate the Mammalian Clock and Energy Metabolism

Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins

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