The role of REV-ERB in NASH

Griffett, Kristine; Hayes, Matthew; Boeckman, Michael P; Burris, Thomas P.

doi:10.1038/s41401-022-00883-w

Cited by 10 publications

(7 citation statements)

References 105 publications

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“…Additional studies have shown that circadian regulation can alleviate inflammatory responses under physiological and pathological conditions, such as limiting hepatocyte inflammation by daily regulation of oxidative phosphorylation ( Bai L et al, 2021 ). Rev-erbα, a transcriptional repressor regulated by a ligand, is expected to be developed as a therapeutic agent for NASH and other liver diseases ( Sato et al, 2020 ; Griffett et al, 2022 ). Such studies help predict the circadian pattern of drug metabolism genes in patients with inflammatory conditions ( Figure 4 ).…”

Section: Introductionmentioning

confidence: 99%

Inflammatory signaling on cytochrome P450-mediated drug metabolism in hepatocytes

Wang

Rao²,

Tan³

et al. 2022

Front. Pharmacol.

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Cytochrome P450 (CYP450) enzymes are membrane-bound blood proteins that are vital to drug detoxification, cell metabolism, and homeostasis. CYP450s belonging to CYP families 1–3 are responsible for nearly 80% of oxidative metabolism and complete elimination of approximately 50% of all common clinical drugs in humans liver hepatocytes. CYP450s can affect the body’s response to drugs by altering the reaction, safety, bioavailability, and toxicity. They can also regulate metabolic organs and the body’s local action sites to produce drug resistance through altered drug metabolism. Genetic polymorphisms in the CYP gene alone do not explain ethnic and individual differences in drug efficacy in the context of complex diseases. The purpose of this review is to summarize the impact of new inflammatory-response signaling pathways on the activity and expression of CYP drug-metabolizing enzymes. Included is a summary of recent studies that have identified drugs with the potential to regulate drug-metabolizing enzyme activity. Our goal is to inspire the development of clinical drug treatment processes that consider the impact of the inflammatory environment on drug treatment, as well as provide research targets for those studying drug metabolism.

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Section: Introductionmentioning

confidence: 99%

Inflammatory signaling on cytochrome P450-mediated drug metabolism in hepatocytes

Wang

Rao²,

Tan³

et al. 2022

Front. Pharmacol.

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“…In liver circadian rhythms, hepatocytes are the peripheral clock that negatively impacts metabolism and overall health 180 . However, the function of REV-ERB can help restore the synchronization of liver clocks, which are frequently disturbed in conditions such as NAFLD, NASH, and metabolic syndrome 181 . In contrast to other nuclear receptors, REV-ERBs function as transcriptional repressors, attracting corepressors when their natural ligand, the iron-centered porphyrin heme, is present 182 , 183 .…”

Section: Rev-erb and Hnf4αmentioning

confidence: 99%

“…In contrast to other nuclear receptors, REV-ERBs function as transcriptional repressors, attracting corepressors when their natural ligand, the iron-centered porphyrin heme, is present 182 , 183 . REV-ERB is a recognized inflammatory regulator that directly regulates IL-1β, IL-6, TNFα, and the NOD-like receptor protein 3 (NLRP3) inflammasome 181 . NLRP3 activation occurs in NAFLD and increases liver inflammation and fibrosis in mouse NASH model 184 , 185 .…”

Section: Rev-erb and Hnf4αmentioning

confidence: 99%

The Role of Nuclear Receptors in the Pathogenesis and Treatment of Non-alcoholic Fatty Liver Disease

Yang,

Danzeng,

Liu

et al. 2024

Int. J. Biol. Sci.

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Non-alcoholic fatty liver disease (NAFLD) is a global health burden closely linked to insulin resistance, obesity, and type 2 diabetes. The complex pathophysiology of NAFLD involves multiple cellular pathways and molecular factors. Nuclear receptors (NRs) have emerged as crucial regulators of lipid metabolism and inflammation in NAFLD, offering potential therapeutic targets for NAFLD. Targeting PPARs and FXRs has shown promise in ameliorating NAFLD symptoms and halting disease progression. However, further investigation is needed to address side effects and personalize therapy approaches. This review summarizes the current understanding of the involvement of NRs in the pathogenesis of NAFLD and explores their therapeutic potential. We discuss the role of several NRs in modulating lipid homeostasis in the liver, including peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), farnesoid X receptors (FXRs), REV-ERB, hepatocyte nuclear factor 4α (HNF4α), constitutive androstane receptor (CAR) and pregnane X receptor (PXR).The expanding knowledge of NRs in NAFLD offers new avenues for targeted therapies, necessitating exploration of novel treatment strategies and optimization of existing approaches to combat this increasingly prevalent disease.

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“… 167 Another study using a high-calorie diet fed genetically obese mice showed that REV-ERB pan-agonists inhibited fibrosis, suggesting a direct role of REV-ERBs in regulating MASLD/MASH pathogenesis. 168 , 169 REV-ERBs also regulate different facets of liver inflammation, including inflammasome activation and T-helper 17 (Th17) cell activation, which are key players in MASH progression. 168 Although a putative REV-ERB agonist SR9009 is available as a dietary supplement, there are no ongoing clinical trials targeting REV-ERB for MASLD/MASH therapy.…”

Section: Circadian Nrsmentioning

confidence: 99%

“… 168 , 169 REV-ERBs also regulate different facets of liver inflammation, including inflammasome activation and T-helper 17 (Th17) cell activation, which are key players in MASH progression. 168 Although a putative REV-ERB agonist SR9009 is available as a dietary supplement, there are no ongoing clinical trials targeting REV-ERB for MASLD/MASH therapy. Despite the potential benefits of targeting REV-ERBs in MASH, further research is needed to fully elucidate their mechanism of action and evaluate their efficacy and safety in clinical settings.…”

Section: Circadian Nrsmentioning

confidence: 99%

Targeting nuclear receptors for NASH/MASH: From bench to bedside

Sinha

2024

Liver Research

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The role of REV-ERB in NASH

Cited by 10 publications

References 105 publications

Inflammatory signaling on cytochrome P450-mediated drug metabolism in hepatocytes

Inflammatory signaling on cytochrome P450-mediated drug metabolism in hepatocytes

The Role of Nuclear Receptors in the Pathogenesis and Treatment of Non-alcoholic Fatty Liver Disease

Targeting nuclear receptors for NASH/MASH: From bench to bedside

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