Basal mTORC2 activity and expression of its components display diurnal variation in mouse perivascular adipose tissue

Drägert, Katja; Bhattacharya, Indranil; Hall, Michael N.; Humar, Rok; Battegay, Edouard; Haas, Elvira

doi:10.1016/j.bbrc.2016.03.102

Cited by 7 publications

(5 citation statements)

References 30 publications

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“…For example, feeding/fasting cycles in animals can be driven by the circadian oscillator in the brain and may, in turn, drive rhythmic TOR activity in peripheral tissues through changing the levels of glucose and hormones, but this does not provide us with an insight into the potential intrinsic rhythmicity of the TOR pathway in individual cells. TOR activity has been reported to be rhythmic in tissues removed from animals in light/dark cycles [38][39][40][41][42][43], or in constant darkness [44][45][46], but these TOR rhythms have not been shown to be cell-autonomous.…”

Section: Is Tor Activity Rhythmic?mentioning

confidence: 99%

The Case for the Target of Rapamycin Pathway as a Candidate Circadian Oscillator

Lakin-Thomas

2023

IJMS

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The molecular mechanisms that drive circadian (24 h) rhythmicity have been investigated for many decades, but we still do not have a complete picture of eukaryotic circadian systems. Although the transcription/translation feedback loop (TTFL) model has been the primary focus of research, there are many examples of circadian rhythms that persist when TTFLs are not functioning, and we lack any good candidates for the non-TTFL oscillators driving these rhythms. In this hypothesis-driven review, the author brings together several lines of evidence pointing towards the Target of Rapamycin (TOR) signalling pathway as a good candidate for a non-TTFL oscillator. TOR is a ubiquitous regulator of metabolism in eukaryotes and recent focus in circadian research on connections between metabolism and rhythms makes TOR an attractive candidate oscillator. In this paper, the evidence for a role for TOR in regulating rhythmicity is reviewed, and the advantages of TOR as a potential oscillator are discussed. Evidence for extensive feedback regulation of TOR provides potential mechanisms for a TOR-driven oscillator. Comparison with ultradian yeast metabolic cycles provides an example of a potential TOR-driven self-sustained oscillation. Unanswered questions and problems to be addressed by future research are discussed.

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Section: Is Tor Activity Rhythmic?mentioning

confidence: 99%

The Case for the Target of Rapamycin Pathway as a Candidate Circadian Oscillator

Lakin-Thomas

2023

IJMS

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“…Moreover, protein 70 S6 kinase 1 (S6K1), a key factor in the mTOR pathway, is able to phosphorylate BMAL1 in circadian rhythm, thus affects the CLOCK:BMAL1-mediated circadian translational machinery [ 223 ]. In mouse adipose tissue, mRNA expression of Rictor and mTOR peaks during the day and troughs at night, while Rictor-adipose-tissue-specific KO mice have altered circadian genes expression in adipose tissue and non-dipping hypertension development [ 224 , 225 ].…”

Section: Oxidative Stress and Circadian Rhythmmentioning

confidence: 99%

Circadian Rhythm in Adipose Tissue: Novel Antioxidant Target for Metabolic and Cardiovascular Diseases

Man¹,

Xia²,

Li³

2020

Antioxidants

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Obesity is a major risk factor for most metabolic and cardiovascular disorders. Adipose tissue is an important endocrine organ that modulates metabolic and cardiovascular health by secreting signaling molecules. Oxidative stress is a common mechanism associated with metabolic and cardiovascular complications including obesity, type 2 diabetes, and hypertension. Oxidative stress can cause adipose tissue dysfunction. Accumulating data from both humans and experimental animal models suggest that adipose tissue function and oxidative stress have an innate connection with the intrinsic biological clock. Circadian clock orchestrates biological processes in adjusting to daily environmental changes according to internal or external cues. Recent studies have identified the genes and molecular pathways exhibiting circadian expression patterns in adipose tissue. Disruption of the circadian rhythmicity has been suggested to augment oxidative stress and aberrate adipose tissue function and metabolism. Therefore, circadian machinery in the adipose tissue may be a novel therapeutic target for the prevention and treatment of metabolic and cardiovascular diseases. In this review, we summarize recent findings on circadian rhythm and oxidative stress in adipose tissue, dissect the key components that play a role in regulating the clock rhythm, oxidative stress and adipose tissue function, and discuss the potential use of antioxidant treatment on metabolic and cardiovascular diseases by targeting the adipose clock.

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“…mTOR activity in vivo is induced by the abundance of nutrients and gradually decreases during fasting. However, food-independent rhythmicity in activity and expression of the mTORC1 complex members has been observed in the SCN and liver, cardiac and skeletal muscles, adipocytes, and retinal photoreceptors but not in the intestine or lung [126][127][128][129][130][131][132][133][134]. In the mouse brain, mTORC1 activities exhibit daily alterations in the arcuate nucleus, hippocampus, and the frontal cortex [130,135,136], all regions that manage circadian rhythms, feeding, learning, memory, and emotions.…”

Section: Mtor Signaling and The Circadian Rhythmmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors as Molecular Links between Caloric Restriction and Circadian Rhythm

Duszka

Wahli

2020

Nutrients

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The circadian rhythm plays a chief role in the adaptation of all bodily processes to internal and environmental changes on the daily basis. Next to light/dark phases, feeding patterns constitute the most essential element entraining daily oscillations, and therefore, timely and appropriate restrictive diets have a great capacity to restore the circadian rhythm. One of the restrictive nutritional approaches, caloric restriction (CR) achieves stunning results in extending health span and life span via coordinated changes in multiple biological functions from the molecular, cellular, to the whole–body levels. The main molecular pathways affected by CR include mTOR, insulin signaling, AMPK, and sirtuins. Members of the family of nuclear receptors, the three peroxisome proliferator–activated receptors (PPARs), PPARα, PPARβ/δ, and PPARγ take part in the modulation of these pathways. In this non-systematic review, we describe the molecular interconnection between circadian rhythm, CR–associated pathways, and PPARs. Further, we identify a link between circadian rhythm and the outcomes of CR on the whole–body level including oxidative stress, inflammation, and aging. Since PPARs contribute to many changes triggered by CR, we discuss the potential involvement of PPARs in bridging CR and circadian rhythm.

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Basal mTORC2 activity and expression of its components display diurnal variation in mouse perivascular adipose tissue

Cited by 7 publications

References 30 publications

The Case for the Target of Rapamycin Pathway as a Candidate Circadian Oscillator

The Case for the Target of Rapamycin Pathway as a Candidate Circadian Oscillator

Circadian Rhythm in Adipose Tissue: Novel Antioxidant Target for Metabolic and Cardiovascular Diseases

Peroxisome Proliferator-Activated Receptors as Molecular Links between Caloric Restriction and Circadian Rhythm

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