Lipid metabolism around the body clocks

Progress in Lipid Research, Journal Year: 2023, Volume and Issue: 91, P. 101235 - 101235

Published: May 15, 2023

Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations lipid are responsible for the development various pathologies comprising metabolic syndrome, obesity, type 2 diabetes. Accumulating evidence suggests that circadian oscillators, operative most cells our body, coordinate temporal homeostasis. In this review we summarize current knowledge on regulation digestion, absorption, transportation, biosynthesis, catabolism, storage. Specifically, focus molecular interactions between functional clockwork biosynthetic pathways major classes cholesterol, fatty acids, triacylglycerols, glycerophospholipids, glycosphingolipids, sphingomyelins. A growing body epidemiological studies associate a socially imposed misalignment common modern society incidence disorders, however disruption rhythms connection has only been recently revealed. Here, highlight recent unravel mechanistic link intracellular clocks, homeostasis diseases based animal models clock innovative translational humans. We also discuss perspectives manipulating oscillators as potentially powerful approach preventing managing disorders human patients.

Language: Английский

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Targeting immune cell recruitment in atherosclerosis

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 21(11), P. 824 - 840

Published: April 25, 2024

Language: Английский

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Basic helix–loop–helix ARNT like 1 regulates the function of immune cells and participates in the development of immune-related diseases

Burns & Trauma, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 1, 2025

The circadian clock is an internal timekeeper system that regulates biological processes through a central and peripheral clocks controlling various genes. Basic helix-loop-helix ARNT-like 1 (BMAL1), also known as aryl hydrocarbon receptor nuclear translocator-like protein (ARNTL1), key component of the clock. deletion BMAL1 alone can abolish rhythms human body. plays critical role in immune cell function. Dysregulation linked to immune-related diseases such autoimmune diseases, infectious cancer, vice versa. This review highlights significant governing cells, including their development, differentiation, migration, homing, metabolism, effector functions. study explores how dysregulation have far-reaching implications potentially contribute onset sepsis, trauma. Furthermore, this discusses treatments for target disorders. Understanding impact on function provide insights into pathogenesis help development more effective treatment strategies. Targeting has been demonstrated achieve good efficacy indicating its promising potential targetable therapeutic these diseases.

Language: Английский

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Mammalian circadian systems: Organization and modern life challenges

Acta Physiologica, Journal Year: 2020, Volume and Issue: 231(3)

Published: Sept. 1, 2020

Abstract Humans and other mammalian species possess an endogenous circadian clock system that has evolved in adaptation to periodically reoccurring environmental changes drives rhythmic biological functions, as well behavioural outputs with approximately 24‐hour period. In mammals, body clocks are hierarchically organized, encompassing a so‐called pacemaker the hypothalamic suprachiasmatic nucleus (SCN), non‐SCN brain peripheral clocks, cell‐autonomous oscillators within virtually every cell type. A functional machinery on molecular level, alignment among synchronization between exogenous cycles been shown be crucial for our health well‐being. Yet, modern life constantly poses widespread challenges internal example artificial lighting, shift work trans‐meridian travel, potentially leading disruption or misalignment emergence of associated diseases. For instance many us experience mismatch sleep timing free days (social jetlag) everyday lives without being aware consequences may arise from such chronic misalignment, Hence, this review provides overview organization built‐up system, its interactions outside world, pathologies arising misalignment.

Language: Английский

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Defining circadian disruption in neurodegenerative disorders

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(19)

Published: Sept. 30, 2021

Neurodegenerative diseases encompass a large group of conditions that are clinically and pathologically diverse yet linked by shared pathology misfolded proteins. The accumulation insoluble aggregates is accompanied progressive loss vulnerable neurons. For some patients, the symptoms motor focused (ataxias), while others experience cognitive psychiatric (dementias). Among neurodegenerative disruption sleep/wake cycle occurs early in trajectory disease may be risk factor for development. In many cases, timing sleep other rhythmic physiological markers immediately raises possibility neurodegeneration-driven circadian system. aim this Review to summarize evidence supporting hypothesis core symptom within diseases, including Alzheimer's disease, Huntington's Parkinson's discuss latest progress field. discusses processes disrupt structure function system describes circadian-based interventions as well timed drug treatments improve wide range associated with disorders. It also identifies key gaps our knowledge.

Language: Английский

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Redox Biology of Melatonin: Discriminating Between Circadian and Noncircadian Functions

Antioxidants and Redox Signaling, Journal Year: 2022, Volume and Issue: 37(10-12), P. 704 - 725

Published: Jan. 12, 2022

Melatonin has not only to be seen as a regulator of circadian clocks. In addition its chronobiotic functions, it displays other actions, especially in cell protection. This includes antioxidant, anti-inflammatory, and mitochondria-protecting effects. Although protection is also modulated by the system, respective actions melatonin can distinguished differ with regard dose requirements therapeutic settings. It aim this article outline these differences terms function, signaling, dosage. Focus been placed on both nexus dissecting properties between noncircadian mechanisms. consider details beyond classic view melatonin's role, such widespread synthesis extrapineal tissues, formation mitochondria, effects mitochondrial permeability transition pore, secondary for example, via upregulation sirtuins regulating noncoding RNAs, microRNAs. The relevance findings, connections functions shed light regulation inflammation, including macrophage/microglia polarization, damage-associated molecular patterns, avoidance cytokine storms, numerous consequences antioxidative protection, that is, aspects high actuality deadly viral bacterial diseases. Antioxid. Redox Signal. 37, 704–725.

Language: Английский

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Disruption of Circadian Rhythm Genes in Obstructive Sleep Apnea Patients—Possible Mechanisms Involved and Clinical Implication

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(2), P. 709 - 709

Published: Jan. 10, 2022

Obstructive sleep apnea (OSA) is a chronic condition characterized by recurrent pauses in breathing caused the collapse of upper airways, which results intermittent hypoxia and arousals during night. The disorder associated with vast number comorbidities affecting different systems, including cardiovascular, metabolic, psychiatric, neurological complications. Due to abnormal architecture, OSA patients are at high risk circadian clock disruption, as has been reported several recent studies. affects almost all daily behavioral patterns, well plethora physiological processes, might be one key factors contributing An intricate interaction between may further affect these strong foundation on molecular level. Recent studies revealed an hypoxia-inducible factor 1 (HIF-1), regulator oxygen metabolism, elements clocks. This relationship base structure involved elements, HIF-1 PER, CLOCK, BMAL, belong same Per-Arnt-Sim domain family. Therefore, this review summarizes available knowledge mechanism disruption its influence development progression comorbidities.

Language: Английский

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Single‐cell transcriptomic analysis reveals circadian rhythm disruption associated with poor prognosis and drug‐resistance in lung adenocarcinoma

Journal of Pineal Research, Journal Year: 2022, Volume and Issue: 73(1)

Published: April 18, 2022

Circadian rhythm disruption (CRD) represents a major contributor to tumor proliferation. Nonetheless, the role of CRD in clinical prediction cancer outcomes has not been well studied. In this study, we developed computational algorithm, which was implemented an open-source R package CRDscore, define intratumoral status circadian three representative single-cell RNA-seq data sets lung adenocarcinoma. We found that malignant cells with high CRDscore were characterized by activation glycolysis and epithelial-mesenchymal transition pathways. Furthermore, cell communication analysis indicated played pivotal T exhaustion, may be responsible for poor prognosis malignancy. then validated findings public bulk transcriptome datasets involving 22 types. Cox regression revealed valuable prognostic biomarker. A model containing 23 circadian-related genes performed predicting immunotherapeutic 14 independent cohorts. Importantly, decreased detect RNA sequencing on H1299 melatonin treatment. Meanwhile, downregulated expression level SNAIL TWIST, contributed invasive phenotype. conclusion, study provides novel framework characterizing using transcriptomic further confirmed molecular mechanisms underlying metabolic reprogramming exhaustion under CRD. The better understanding provide new possibilities incorporating "anticancer approaches based clocks" into treatment protocols precision medicine.

Language: Английский

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Circadian rhythm disruption in critically ill patients

Acta Physiologica, Journal Year: 2023, Volume and Issue: 238(1)

Published: March 14, 2023

Abstract Patients admitted to the intensive care unit (ICU) are in need of continuous organ replacement strategies and specialized care, for example because neurological dysfunction, cardio‐pulmonary instability, liver or kidney failure, trauma, hemorrhagic septic shock even preterm birth. The 24‐h nursing interventions provided critically ill patients significantly limit resting and/or recovery phases. Consecutively, patient's endogenous circadian rhythms misaligned disrupted, which turn may interfere with their critical condition. A more thorough understanding complex interactions effectors tissue‐specific molecular clocks could therefore serve as potential means enhancing personalized treatment patients, conceivably restoring network thus accelerating physical neurocognitive recovery. This review addresses overarching issue how affected disturbed newborns adults ICU, whether conflicting external environmental cues ICU environment further promote disruption severity illness. We direct special attention influence cell‐type specific on dysfunctions such brain pneumonia‐ ventilator‐associated lung inflammation, cardiovascular shock. Finally, we address rhythm stabilization enhance accelerate clinical

Language: Английский

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Complex gene-dependent and-independent mechanisms control daily rhythms of hematopoietic cells

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117803 - 117803

Published: Jan. 2, 2025

Language: Английский

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