REV-ERB nuclear receptors in the suprachiasmatic nucleus control circadian period and restrict diet-induced obesity

Adlanmérini, Marine; Krusen, Brianna M.; Nguyen, Hoang Cong; Teng, Clare W; Woodie, Lauren N.; Tackenberg, Michael C.; Geisler, C. Daniel; Gaisinsky, Jane; Peed, Lindsey C.; Carpenter, Bryce J.; Hayes, Matthew R.; Lazar, Mitchell A.

doi:10.1126/sciadv.abh2007

Cited by 23 publications

(24 citation statements)

References 61 publications

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“…Chronic jet lag induces spontaneous hepatocelluar carinoma in mice (16). A recent study supported the desynchrony hypothesis by showing that mice whose central clock ran with a 21 hours day due to genetic loss of REV-ERBs developed metabolic dysfunction, including fatty liver, that could be rescued by matching the environmental light/dark cycle to the endogenous clock (53). Timedependent changes in proliferation and DNA damage were observed in transgenic c-myc/transforming growth factor (TGFα) that develop hepatocellular carcinoma (HCC) (54), providing a rationale for optimizing the timing of radiotherapy (55).…”

Section: Translating Circadian Insights Into Therapeutic Strategiesmentioning

confidence: 94%

“…16 A recent study supported the desynchrony hypothesis by showing that mice whose central clock ran with a 21 hours' day due to genetic loss of REV-ERBs developed metabolic dysfunction, including fatty liver, that could be rescued by matching the environmental light/dark cycle to the endogenous clock. 53 Time-dependent changes in proliferation and DNA damage were observed in transgenic c-myc/transforming growth factor-α that develop HCC, 54 providing a rationale for optimizing the timing of radiotherapy. 55 Future studies are needed to determine whether the synchronization of environmental timekeepers and endogenous clocks could improve fatty liver diseases.…”

Section: Translating Circadian Insights Into Therapeutic Strategiesmentioning

confidence: 99%

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Circadian Regulation of Gene Expression and Metabolism in the Liver

Guan

Lazar

2022

Semin Liver Dis

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Circadian rhythms are approximately 24-hour cycles of variation in physiological processes, gene expression, and behavior. They result from the interplay of internal biological clocks with daily environmental rhythms, including light/dark and feeding/fasting. 24-hour rhythms of liver metabolic processes have been known for almost 100 years. Modern studies reveal that, like metabolism, hepatic gene expression is highly rhythmic. Genetic or environmental changes can disrupt the circadian rhythms of the liver, leading to metabolic disorders and hepatocellular carcinoma. In this review, we summarize the current understanding of mechanisms regulating rhythmic gene expression in liver, highlighting the roles of transcription factors that comprise the core clock molecular as well as noncanonical regulators. We emphasize the plasticity of circadian rhythms in the liver as it responds to multiple inputs from the external and internal environments as well as the potential of circadian medicine to impact liver-related diseases.

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Section: Translating Circadian Insights Into Therapeutic Strategiesmentioning

confidence: 94%

Section: Translating Circadian Insights Into Therapeutic Strategiesmentioning

confidence: 99%

Circadian Regulation of Gene Expression and Metabolism in the Liver

Guan

Lazar

2022

Semin Liver Dis

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“…By contrast, an SCN-specific Rev-erbα / β double knockout shifted metabolic and behavioral rhythms by approximately three hours, entraining affected mouse models to a roughly 21 h day. SCN Rev-erbα / β deletion also rendered mice significantly more susceptible to acute weight gain when fed a high-fat diet [ 24 ], indicating that REV-ERBs play an important role in the prevention of diet-induced obesity. Importantly, readjusting the light/dark cycles of affected mice to their endogeneous 21 h clock appeared to rescue the adverse metabolic effects of the SCN Rev-erβ double knockout [ 24 ].…”

Section: Rhythms Of Feeding and Fastingmentioning

confidence: 99%

“…A hallmark of obesity and metabolic disease, however, is a decreased ability to adapt effectively between metabolic states [ 18 , 19 , 20 , 21 ]. Furthermore, when endogenous circadian pacing is at odds with the external environment, this finely tuned mechanism breaks down and has been found to be an important risk factor for a series of disease states including cardiovascular illness, substance use disorder, attention-deficit-hyperactivity disorder (ADHD), and certain psychiatric and neurodegenerative conditions such as dementia, depression, and anxiety in addition to obesity and metabolic disease [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

The Circadian Regulation of Nutrient Metabolism in Diet-Induced Obesity and Metabolic Disease

et al. 2022

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Obesity and other metabolic diseases are major public health issues that are particularly prevalent in industrialized societies where circadian rhythmicity is disturbed by shift work, jet lag, and/or social obligations. In mammals, daylight entrains the hypothalamic suprachiasmatic nucleus (SCN) to a ≈24 h cycle by initiating a transcription/translation feedback loop (TTFL) of molecular clock genes. The downstream impacts of the TTFL on clock-controlled genes allow the SCN to set the rhythm for the majority of physiological, metabolic, and behavioral processes. The TTFL, however, is ubiquitous and oscillates in tissues throughout the body. Tissues outside of the SCN are entrained to other signals, such as fed/fasting state, rather than light input. This system requires a considerable amount of biological flexibility as it functions to maintain homeostasis across varying conditions contained within a 24 h day. In the face of either circadian disruption (e.g., jet lag and shift work) or an obesity-induced decrease in metabolic flexibility, this finely tuned mechanism breaks down. Indeed, both human and rodent studies have found that obesity and metabolic disease develop when endogenous circadian pacing is at odds with the external cues. In the following review, we will delve into what is known on the circadian rhythmicity of nutrient metabolism and discuss obesity as a circadian disease.

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“…A pilot trial showed bright light therapy to reduce cancer-related fatigue and depression [141]. For patients with a non-24-h rhythm, animal models suggest that REV-ERB-targeting agents may provide a promising option for modulating period lengths while also counteracting diet-induced weight gain [160].…”

Section: Zeitgeber Dietmentioning

confidence: 99%

Chronoradiobiology of Breast Cancer: The Time Is Now to Link Circadian Rhythm and Radiation Biology

Nelson

Lombardo

Matlack

et al. 2022

IJMS

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Circadian disruption has been linked to cancer development, progression, and radiation response. Clinical evidence to date shows that circadian genetic variation and time of treatment affect radiation response and toxicity for women with breast cancer. At the molecular level, there is interplay between circadian clock regulators such as PER1, which mediates ATM and p53-mediated cell cycle gating and apoptosis. These molecular alterations may govern aggressive cancer phenotypes, outcomes, and radiation response. Exploiting the various circadian clock mechanisms may enhance the therapeutic index of radiation by decreasing toxicity, increasing disease control, and improving outcomes. We will review the body’s natural circadian rhythms and clock gene-regulation while exploring preclinical and clinical evidence that implicates chronobiological disruptions in the etiology of breast cancer. We will discuss radiobiological principles and the circadian regulation of DNA damage responses. Lastly, we will present potential rational therapeutic approaches that target circadian pathways to improve outcomes in breast cancer. Understanding the implications of optimal timing in cancer treatment and exploring ways to entrain circadian biology with light, diet, and chronobiological agents like melatonin may provide an avenue for enhancing the therapeutic index of radiotherapy.

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REV-ERB nuclear receptors in the suprachiasmatic nucleus control circadian period and restrict diet-induced obesity

Cited by 23 publications

References 61 publications

Circadian Regulation of Gene Expression and Metabolism in the Liver

Circadian Regulation of Gene Expression and Metabolism in the Liver

The Circadian Regulation of Nutrient Metabolism in Diet-Induced Obesity and Metabolic Disease

Chronoradiobiology of Breast Cancer: The Time Is Now to Link Circadian Rhythm and Radiation Biology

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