Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: primary and secondary gene responses with links to disease progression

Toxicological Sciences, Год журнала: 2024, Номер 200(2), С. 324 - 345

Опубликована: Май 6, 2024

Constitutive androstane receptor (CAR, Nr1i3), a liver nuclear and xenobiotic sensor, induces drug, steroid, lipid metabolizing enzymes, stimulates hypertrophy hyperplasia, ultimately, hepatocellular carcinogenesis. The mechanisms linking early CAR responses to later disease development are poorly understood. Here we show that exposure of CD-1 mice TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene), halogenated xenochemical selective agonist ligand, pericentral steatosis marked by hepatic accumulation cholesterol neutral lipid, elevated circulating alanine aminotransferase, indicating hepatocyte damage. TCPOBOP-induced was weaker in the region but stronger periportal females compared with males. Early (1 day) transcriptional were enriched for CAR-bound primary response genes, lipogenesis metabolism oxidative stress protection pathways; late (2 weeks) included many binding-independent secondary enrichment macrophage activation, immune response, cytokine reactive oxygen species production. Late upstream regulators specific TCPOBOP-exposed male linked proinflammatory carcinoma progression. administered weekly using high corn oil vehicle induced carbohydrate-responsive transcription factor (MLXIPL)-regulated target dysregulated mitochondrial respiratory translation regulatory pathways, more advanced pathology. Overall, recapitulates histological gene expression changes characteristic emerging steatotic disease, including nonparenchymal cells indicative transition state. Upstream both genes include novel biomarkers foreign chemical-induced metabolic dysfunction-associated disease.

Язык: Английский

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Identification and functional characterization of a novel cystatin in amphioxus, ancient origin of vertebrate type-2 cystatin homologues

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 277, С. 134429 - 134429

Опубликована: Авг. 7, 2024

Язык: Английский

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Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: Primary and secondary gene responses with links to disease progression

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 20, 2024

Abstract Constitutive Androstane Receptor (CAR, Nr1i3 ), a liver nuclear receptor and xenobiotic sensor, induces drug, steroid lipid metabolizing enzymes, stimulates hypertrophy hyperplasia, ultimately, hepatocellular carcinogenesis. The mechanisms linking early CAR responses to subsequent disease development are poorly understood. Here we show that exposure of CD-1 mice TCPOBOP, halogenated xenochemical selective agonist ligand, pericentral steatosis marked by hepatic accumulation cholesterol neutral lipid, elevated circulating alanine aminotransferase levels, indicating hepatocyte damage. TCPOBOP-induced was weaker in the region but stronger periportal females compared males. Early (1-day) TCPOBOP transcriptional were enriched for CAR-bound primary response genes, metabolism oxidative stress protection pathways; late (2-wk) included many binding-independent secondary with enrichment immune response, macrophage activation, cytokine reactive oxygen species production. Late upstream regulators specific TCPOBOP-exposed male linked pro-inflammatory carcinoma progression. administered weekly using high corn oil vehicle activated carbohydrate-responsive transcription factor (MLXIPL)-regulated target dysregulated mitochondrial respiratory translation regulatory pathways, induced more advanced pathology. Thus, recapitulates histological gene expression changes characteristic emerging steatotic disease, including non-parenchymal cells indicative transition state. Upstream both include novel biomarkers foreign chemical-induced metabolic dysfunction-associated disease.

Язык: Английский

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Impaired fatty acid import or catabolism in macrophages restricts intracellular growth ofMycobacterium tuberculosis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 23, 2024

Abstract Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyzes demonstrate which cannot either import, store or catabolize acids restrict by both common and divergent anti-microbial mechanisms, including increased glycolysis, oxidative stress, production pro-inflammatory cytokines, enhanced autophagy nutrient limitation. also show impaired droplet biogenesis restrictive replication, but induction same fails rescue growth. work expands our understanding how homeostasis impacts macrophage.

Язык: Английский

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Preparation of ceftiofur-encapsulated hen-egg low-density lipoproteins and their antibacterial effects on intracellular Staphylococcus aureus

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 278, С. 134840 - 134840

Опубликована: Авг. 31, 2024

Язык: Английский

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Lipids: Emerging Players of Microglial Biology

Glia, Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Lipids are small molecule immunomodulators that play critical roles in maintaining cellular health and function. Microglia, the resident immune cells of central nervous system, regulate lipid metabolism both extracellular environment within intracellular compartments through various mechanisms. For instance, glycerophospholipids fatty acids interact with protein receptors on microglial surface, such as Triggering Receptor Expressed Myeloid Cells 2, influencing functions like phagocytosis migration. Moreover, cholesterol is essential not only for survival but, along other lipids acids, crucial formation, function, accumulation droplets, which modulate activity inflammatory diseases. Other lipids, including acylcarnitines ceramides, participate signaling pathways microglia. Despite complexity lipidome, a few studies have investigated effects specific classes biology. In this review, we focus major their modulating We also discuss novel analytical techniques characterizing lipidome highlight gaps current knowledge, suggesting new directions future research

Язык: Английский

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Lipids in Equine Airway Inflammation: An Overview of Current Knowledge

Animals, Год журнала: 2024, Номер 14(12), С. 1812 - 1812

Опубликована: Июнь 18, 2024

Mild–moderate and severe equine asthma (MEA SEA) are prevalent inflammatory airway conditions affecting horses of numerous breeds disciplines. Despite extensive research, detailed disease pathophysiology the differences between MEA SEA still not completely understood. Bronchoalveolar lavage fluid cytology, broadly used in clinical practice has limited means to represent status lower airways. Lipidomics is a field science that can be utilized investigating cellular mechanisms cell-to-cell interactions. Studies lipidomics have broad variety foci, which fatty acid lipid mediator profile analyses global been implemented veterinary medicine. As many crucial proinflammatory proresolving mediators lipids, lipidomic studies offer an interesting yet largely unexplored investigate reactions The aim this review article collect summarize findings recent on inflammation.

Язык: Английский

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Life cycle of macrophages in atherosclerotic inflammation progression and resolution: mediators and interventions (narrative review)

Emergency and Critical Care Medicine, Год журнала: 2024, Номер unknown

Опубликована: Авг. 6, 2024

Abstract As one of the pathological causes coronary heart disease, atherosclerosis poses a major threat to human health. Macrophages play an important role in regulating atherosclerotic disease progression. Specifically, inflammation is initiated when low-density lipoproteins infiltrate subcutaneous area and are phagocytosed by macrophages, leading foam cell formation. The subsequent progression or resolution depends on delicate balance between proinflammatory anti-inflammatory mediators. In cases where factors dominate, macrophages tend activate pyroptosis necrosis pathways, resulting release intracellular damage-associated molecular patterns promoting necrotic core formation plaque Conversely, prevail, engage autophagy-mediated lipid metabolism while inhibiting through efferocytosis apoptotic cells. regulatory function can also be understood from perspective their life cycles. Lipid retention within arterial intima its uptake characteristic hallmarks atherosclerosis. pivotal effector cells this process, with distinctive performances decisively determine inflammation. complete cycle plaques encompasses chemotaxis, infiltration, polarization, for metabolic efflux, formation, overload, various forms programmed necrosis, including autophagy, pyroptosis, apoptosis, efferocytosis, facilitate removal limit behavior has rarely been comprehensively addressed previous review articles. This article provides extensive overview entire following response impact resolution. Considering that inflammatory associated atherosclerosis, targeting regulation holds promise therapeutic interventions against atherosclerosis-related cardiovascular diseases.

Язык: Английский

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Current approaches in CRISPR-Cas system for metabolic disorder

Progress in molecular biology and translational science, Год журнала: 2024, Номер unknown, С. 1 - 19

Опубликована: Авг. 16, 2024

Язык: Английский

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Shedding new light on atherosclerosis therapeutics: Nanomedicines targeting atherosclerotic immune microenvironment

Deleted Journal, Год журнала: 2024, Номер 1(3), С. 100043 - 100043

Опубликована: Ноя. 14, 2024

Язык: Английский

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