Potential bidirectional communication between the liver and the central circadian clock in MASLD

npj Metabolic Health and Disease, Journal Year: 2025, Volume and Issue: 3(1)

Published: April 9, 2025

Most aspects of physiology and behaviour fluctuate every 24 h in mammals. These circadian rhythms are orchestrated by an autonomous central clock located the suprachiasmatic nuclei that coordinates timing cellular clocks tissues throughout body. The critical role this system is emphasized increasing evidence associating disruption with diverse pathologies. Accordingly, mounting suggests a bidirectional relationship where misalignment may contribute to liver diseases while alter other tissues. Therefore, pathophysiology broadly impact provide mechanistic framework for understanding targeting metabolic adjust setpoints.

Language: Английский

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Liver Neurobiology: Regulation of Liver Functions by the Nervous System

Seminars in Liver Disease, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

The nervous system plays an important role in the regulation of liver functions during physiological as well pathological conditions. This regulatory effect is based on processing signals transmitted to brain by sensory nerves innervating tissue and other visceral organs humoral pathways transmitting from peripheral tissues organs. Based these signals, modulates metabolism, detoxification, regeneration, repair, inflammation, processes occurring liver. thus determines functional morphological characteristics Liver innervation also mediates influence psychosocial factors functions. aim this review describe complexity bidirectional interactions between characterize mechanisms through which influences function conditions maintains systemic homeostasis.

Language: Английский

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Nuclear receptors: pathophysiological mechanisms and drug targets in liver disease

Gut, Journal Year: 2024, Volume and Issue: 73(9), P. 1562 - 1569

Published: June 11, 2024

Nuclear receptors (NRs) are ligand-dependent transcription factors required for liver development and function. As a consequence, NRs have emerged as attractive drug targets in wide range of diseases. However, dysfunction failure linked to loss hepatocyte identity characterised by deficient NR expression activities. This might at least partly explain why several pharmacological modulators proven insufficiently efficient improve functionality advanced stages diseases such metabolic dysfunction-associated steatotic disease (MASLD). In this perspective, we review the most recent advances hepatic field discuss contribution multiomic approaches our understanding their role molecular organisation an intricated transcriptional regulatory network, well intercellular dialogues interorgan cross-talks. We potential benefit novel therapeutic simultaneously targeting multiple NRs, which would not only reactivate network restore but also impact interplays whose importance control functions is further defined. Finally, highlight need considering individual parameters sex stage NR-based clinical strategies.

Language: Английский

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Combined physical exercise re-synchronizes expression of Bmal1 and REV-ERBα and up-regulates apoptosis and metabolism in the prostate during aging

Life Sciences, Journal Year: 2024, Volume and Issue: 351, P. 122800 - 122800

Published: June 15, 2024

Language: Английский

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Construction of a circadian rhythm-relevant gene signature for hepatocellular carcinoma prognosis, immunotherapy and chemosensitivity prediction

Heliyon, Journal Year: 2024, Volume and Issue: 10(13), P. e33682 - e33682

Published: June 26, 2024

AimsThis study explored the molecular and biologic mechanisms underlying association between circadian rhythm disorders (CRD) increased risk for hepatocellular carcinoma (HCC).BackgroundCRD are linked to HCC, but this limited.ObjectiveThe constructed validated a CRD related gene model as an independent prognostic factor providing insight into linking HCC identifying potential indicators efficacy of immunotherapy anticancer drugs. This helps provide important clues personalized treatment strategies patients.MethodsGene sets correlated with were obtained from Molecular Signatures Database (MSigDB) intersect differentially expressed genes (DEGs) tumor samples control in The Cancer Genome Atlas (TCGA) HCCDB18 Hepatocellular Carcinoma Cell DataBase (HCCDB). was developed by univariate Cox stepwise multivariate analysis. Immune checkpoint blockade (ICB) therapy drugs analyzed using immune dysfunction exclusion (TIDE) pRRophetic, respectively. Seurat determined cell type analyzing single-cell data, malignant cells identified Copykat. To detect mRNA levels model, quantitative real-time polymerase chain reaction (qRT-PCR) carried out.ResultsThe activity tissue significantly lower than that tissue. Subsequently, EZH2, IMPDH2, TYMS SERPINE1 selected construct which prognosis. Notably, low-risk patients had infiltration TIDE scores compared high-risk indicating low may derive more benefit immunotherapy. higher benign epithelial cells.ConclusionsThis presents reveal perspective dependent mechanism cancer, provides indicator understanding preclinical ICB

Language: Английский

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Therapeutic Potential of Honey Against Hepatotoxicity and Renal Toxicity: Insight into Its Mechanisms of Action

Published: Jan. 1, 2024

Language: Английский

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Joint effects of sleep disturbance and renal function impairment on incident new‐onset severe metabolic dysfunction‐associated steatotic liver disease

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 26(10), P. 4724 - 4733

Published: Aug. 8, 2024

Abstract Aim To elucidate the effects of sleep parameters and renal function on risk developing new‐onset severe metabolic dysfunction‐associated steatotic liver disease (MASLD). Materials Methods The primary analysis involved a cohort 305 257 participants. Multivariable Cox models were employed to calculate hazard ratios 95% confidence intervals. Traditional mediation two‐step Mendelian randomization (MR) analyses conducted assess associations mediating roles indicators between MASLD. Results Poor score biomarker (RFS) associated with an increased MASLD (all p trend <0.001). Participants poor patterns highest RFS had 5.45‐fold higher MASLD, compared those healthy lowest ( < 0.001). could explain 10.08% correlations Additionally, MR supported causal link insomnia revealed role chronic kidney in connection risk. Conclusions This study highlights independent combined underscoring bidirectional communication liver–kidney axis providing modifiable strategies for preventing

Language: Английский

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Hepatocellular Carcinoma in Mice Affects Neuronal Activity and Glia Cells in the Suprachiasmatic Nucleus

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2202 - 2202

Published: Sept. 27, 2024

: Chronic liver diseases such as hepatic tumors can affect the brain through liver-brain axis, leading to neurotransmitter dysregulation and behavioral changes. Cancer patients suffer from fatigue, which be associated with sleep disturbances. Sleep is regulated via two interlocked mechanisms: homeostatic regulation circadian system. In mammals, hypothalamic suprachiasmatic nucleus (SCN) key component of It generates rhythms in physiology behavior controls their entrainment surrounding light/dark cycle. Neuron-glia interactions are crucial for functional integrity SCN. Under pathological conditions, oxidative stress compromise these thus timekeeping entrainment. To date, little known about impact peripheral pathologies hepatocellular carcinoma (HCC) on

Language: Английский

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Fisetin Ameliorates Hepatocyte Lipid Droplet Accumulation via Targeting the Rhythmic Protein BMAL1 to Regulate Cell Death-Inducing DNA Fragmentation Factor-α-like Effector C-Mediated Lipid Droplet Fusion

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

High fat diet (HFD) induces the enlargement and accumulation of lipid droplets (LDs) in hepatocytes, thereby influencing homeostasis metabolism. Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC), a surface protein LDs, facilitates their fusion growth, transforming small LDs into larger ones. Lipophagy, selective form autophagy, primarily targets for degradation. Fisetin (FIS), natural dietary flavonoid present various fruits vegetables, has an unclear mechanism reducing LD accumulation. In this study, we observed that FIS significantly ameliorated HFD-induced hepatocytes C57BL/6 mice. further mechanistic studies, revealed FFA enhanced expression CIDEC, which promoted caused them to become larger. The enlarged could not be degraded by ultimately led LDs. Conversely, alleviated inhibiting CIDEC-mediated fusion, resulting smaller facilitated lipophagy. Additionally, studies indicated dysfunction circadian rhythms is closely related our showed HFD disrupted rhythm mouse AML12 cells, while modified disturbances increased core clocks BMAL1 CLOCK. We silenced si-BMAL1 upregulated CIDEC proteins. These data suggested might inhibit enhance hepatocyte lipophagy promoting BMAL1, alleviating cells FFA. study provided novel insights potential utilizing functional food factors mitigate hepatocytes.

Language: Английский

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INFLUENCE OF COMBINED EFFECT OF CONSTANT ILLUMINATION AND CHRONIC ALCOHOL INTOXICATION ON HEPATOCYTE ULTRASTRUCTURE IN MALE AND FEMALE WISTAR RATS

Ulyanovsk Medico-biological Journal, Journal Year: 2023, Volume and Issue: 3, P. 151 - 166

Published: Sept. 27, 2023

Light pollution causes melatonin deficiency and circadian rhythm disruption. Thus, it is associated with hepatopathy. Circadian disruption increases liver damage from alcohol the severity of alcoholism. The aim study was to examine combined effect constant illumination chronic intoxication (CAI) on hepatocyte ultrastructure in male female rats. Materials Methods. carried out 120 80 Wistar outbred rats aged 6 months. experiment lasted 3 weeks. Differences morphological patterns were visually assessed. percentage hepatocytes containing lipid vacuoles calculated. Results. Constant caused allostasis. Hepatocyte edema, mitochondria swelling, karyopyknosis, fatty degeneration, death detected cells rats. above-mentioned pathological changes less severe females. Moreover, collagen layers did not proliferate into tissues So, we can conclude that CAI do lead inflammatory architectural distortion Taking account picture a number biochemical parameters describe its functional state, obtained data gender differences exposed allow us report adaptation stress more successful than ones.

Language: Английский

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