From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease

Annals of Hepatology, Год журнала: 2025, Номер unknown, С. 101777 - 101777

Опубликована: Янв. 1, 2025

Non-alcoholic fatty liver disease (NAFLD), now recognized as metabolic dysfunction-associated steatotic (MASLD), represents a significant and escalating global health challenge. Its prevalence is intricately linked to obesity, insulin resistance, other components of the syndrome. As our comprehension MASLD deepens, it has become evident that this condition extends beyond liver, embodying complex, multi-systemic with hepatic manifestations mirror broader landscape. This comprehensive review delves into critical interplay between gut-liver axis oxidative stress, elucidating their pivotal roles in etiology progression MASLD. Our analysis reveals several key findings: (1) Bile acid dysregulation can trigger stress through enhanced ROS production hepatocytes Kupffer cells, leading mitochondrial dysfunction lipid peroxidation; (2) Gut microbiota dysbiosis disrupts intestinal barrier function, allowing increased translocation endotoxins like LPS, which activate inflammatory pathways TLR4 signaling promote via NADPH oxidase activation; (3) The redox-sensitive transcription factors NF-κB Nrf2 serve crucial mediators axis, regulating responses orchestrating antioxidant defenses; (4) Oxidative stress-induced damage function creates destructive feedback loop, further exacerbating inflammation progression. These findings highlight complex interrelationship pathogenesis, suggesting potential therapeutic targets for management.

Язык: Английский

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Effects of Selected Food Additives on the Gut Microbiome and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Medicina, Год журнала: 2025, Номер 61(2), С. 192 - 192

Опубликована: Янв. 22, 2025

The purpose of this article is to present selected food additives as disruptors normal intestinal homeostasis with a potential impact on the development metabolic dysfunction-associated steatotic liver disease (MASLD). A comprehensive literature search was conducted in three major electronic databases: PubMed, ScienceDirect, and Google Scholar. MASLD prevalent condition that closely related global rise obesity. Its pathogenesis multifactorial, genetic, environmental, factors playing key role. “multiple-hit” hypothesis suggests Western-style diet, rich ultra-processed foods, saturated fats, additives, combined low physical activity, contributes obesity, which promotes lipid accumulation liver. Recent studies underscore role impaired MASLD. Food including preservatives, emulsifiers, sweeteners, affect gut health function. Selected preservatives inhibit pathogenic microorganisms but disrupt microbiota, leading changes permeability dysfunction. Some emulsifiers thickeners can cause inflammation alter microbiome, contributing steatosis. Furthermore, use sweeteners such sucralose aspartame has been linked metabolism microbial composition, turn disorders.

Язык: Английский

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Gender Differences in Insulin Resistance: New Knowledge and Perspectives

Current Issues in Molecular Biology, Год журнала: 2023, Номер 45(10), С. 7845 - 7861

Опубликована: Сен. 27, 2023

Insulin resistance is the main mechanism in a whole series of pathological conditions, which are not only metabolic interest but also systemic type. This phenomenon means that body’s cells become less sensitive to hormone insulin, leading higher levels insulin blood. can be found both men and women particular, latter, it mainly after menopause. Premenopause, hormonal fluctuations during menstrual cycle, presence estrogen affect sensitivity. Androgens, such as testosterone, typically contribute resistance. In sexes, different human body types distribution location fat, influencing development diabetes cardiovascular disease. associated with some neurological neurogenerative disorders, polycystic ovary syndrome, atherosclerosis, neoplastic pathologies. A healthy lifestyle, including regular physical activity, balanced diet, self-maintenance, help prevent onset resistance, regardless gender, although habits between greatly implementation preventative guidelines fighting manifestations this disorder. review may shed light on gender differences diseases by placing necessary focus personalized medical management inspiring differentiated therapeutic approaches.

Язык: Английский

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The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease

Cell Metabolism, Год журнала: 2023, Номер 35(11), С. 1852 - 1871

Опубликована: Ноя. 1, 2023

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an unabated risk factor for end-stage diseases with no available therapies. Dysregulated immune responses are critical culprits of MASLD pathogenesis. Independent contributions from either the innate or adaptive arms system their unidirectional interplay commonly studied in MASLD. However, bidirectional communication between and systems its impact on remain insufficiently understood. Given that both cells indispensable development progression inflammation MASLD, elucidating pathogenic stemming these two holds potential novel therapeutics Here, we review cell types pathways influence pathogenesis highlight pharmacologic approaches to combat based current knowledge this crosstalk.

Язык: Английский

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Sex difference in human diseases: mechanistic insights and clinical implications

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 10, 2024

Abstract Sex characteristics exhibit significant disparities in various human diseases, including prevalent cardiovascular cancers, metabolic disorders, autoimmune and neurodegenerative diseases. Risk profiles pathological manifestations of these diseases notable variations between sexes. The underlying reasons for sex encompass multifactorial elements, such as physiology, genetics, environment. Recent studies have shown that body systems demonstrate sex-specific gene expression during critical developmental stages editing processes. These genes, differentially expressed based on different sex, may be regulated by androgen or estrogen-responsive thereby influencing the incidence presentation cardiovascular, oncological, metabolic, immune, neurological across However, despite existence differences patients with treatment guidelines predominantly rely male data due to underrepresentation women clinical trials. At present, there exists a substantial knowledge gap concerning mechanisms treatments diverse Therefore, this review aims elucidate advances examining epidemiological factors, pathogenesis, innovative progress accordance distinctive risk each disease provide new theoretical practical basis further optimizing individualized improving patient prognosis.

Язык: Английский

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From MASH to HCC: the role of Gas6/TAM receptors

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Янв. 17, 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is the replacement term for what used to be called nonalcoholic (NASH). It characterized by inflammation and injury of liver in presence cardiometabolic risk factors may eventually result development hepatocellular carcinoma (HCC), most common form primary cancer. Several pathogenic mechanisms are involved transition from MASH HCC, encompassing metabolic injury, inflammation, immune dysregulation fibrosis. In this context, Gas6 (Growth Arrest-Specific 6) TAM (Tyro3, Axl, MerTK) receptors play important roles. The Gas6/TAM family modulation lipid metabolism, fibrosis, tumor progression metastasis, processes which an role pathophysiology acute chronic diseases. review, we discuss MASH-associated HCC potential involvement system disease progression. addition, since therapeutic strategies limited, also speculate regarding possible future treatments involving targeting or receptors.

Язык: Английский

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Gut Microbiota at the Crossroad of Hepatic Oxidative Stress and MASLD

Antioxidants, Год журнала: 2025, Номер 14(1), С. 56 - 56

Опубликована: Янв. 6, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic condition marked by excessive lipid accumulation in hepatic tissue. This disorder can lead to range of pathological outcomes, including metabolic steatohepatitis (MASH) and cirrhosis. Despite extensive research, the molecular mechanisms driving MASLD initiation progression remain incompletely understood. Oxidative stress peroxidation are pivotal "multiple parallel hit model", contributing cell death tissue damage. Gut microbiota plays substantial role modulating oxidative through multiple pathways: impairing intestinal barrier, which results bacterial translocation inflammation; modifying bile acid structure, impacts signaling cascades involved lipidic metabolism; influencing hepatocytes' ferroptosis, form programmed death; regulating trimethylamine N-oxide (TMAO) activating platelet function, both recently identified as pathogenetic factors MASH progression. Moreover, various exogenous impact gut its involvement MASLD-related stress, such air pollution, physical activity, cigarette smoke, alcohol, dietary patterns. manuscript aims provide state-of-the-art overview focused on intricate interplay between microbiota, peroxidation, pathogenesis, offering insights into potential strategies prevent associated complications.

Язык: Английский

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Non-alcoholic fatty liver disease: Immunological mechanisms and current treatments

World Journal of Gastroenterology, Год журнала: 2023, Номер 29(32), С. 4831 - 4850

Опубликована: Авг. 24, 2023

Non-alcoholic fatty liver disease (NAFLD) causes significant global burden and is a leading cause of mortality. NAFLD induces myriad aberrant changes in hepatocytes at both the cellular molecular level. Although spectrum widely recognised, precise triggers for progression are still to be fully elucidated. Furthermore, propagation cirrhosis poorly understood. Whilst some progress terms treatment options have been explored, an incomplete understanding hepatic alterations limits their clinical utility. We therefore reviewed key pathways responsible pathogenesis such as innate adaptative immunity, lipotoxicity fibrogenesis, highlighted current trials patients.

Язык: Английский

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The PD-1/PD-L1 Axis in the Biology of MASLD

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3671 - 3671

Опубликована: Март 25, 2024

Metabolic Dysfunction-Associated Steatotic Liver (MASL), previously named nonalcoholic fatty liver (NAFL), is a multifactorial disease in which metabolic, genetic, and environmental risk factors play predominant role. Obesity type 2 diabetes act as triggers of the inflammatory response, contributes to progression MASL Steatohepatitis development hepatocellular carcinoma. In liver, several parenchymal, nonparenchymal, immune cells maintain immunological homeostasis, different regulatory pathways balance activation innate adaptative system. PD-1/PD-L1 signaling acts, maintenance between responses tissue promoting self-tolerance through modulation activated T cells. Recently, PD-1 has received much attention for its roles inducing an exhausted phenotype, tumor escape from responses. Indeed, MASLD, excessive fat accumulation dysregulates system, increasing cytotoxic lymphocytes decreasing their cytolytic activity. this context, exacerbate damage promote progression. The aim review illustrate main pathogenetic mechanisms by system promotes MASLD transition HCC, well discuss possible therapeutic applications target therapy activate reinvigorate surveillance against cancer.

Язык: Английский

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Pathogenetic development, diagnosis and clinical therapeutic approaches for liver metastasis from colorectal cancer (Review)

International Journal of Oncology, Год журнала: 2025, Номер 66(3)

Опубликована: Фев. 14, 2025

Colorectal cancer (CRC) is a prevalent malignancy and significant proportion of patients with CRC develop liver metastasis (CRLM), which major contributor to CRC‑related mortality. The present review aimed comprehensively examine the pathogenetic development diagnosis CRLM clinical therapeutic approaches for treatment this disease. molecular mechanisms underlying were discussed, including role tumour microenvironment epithelial‑mesenchymal transition. also highlighted importance early detection current challenges in predicting CRLM. Various strategies reviewed, surgical resection, chemotherapy immunotherapy, potential novel therapies, such as selective internal radiation therapy Traditional Chinese Medicine. Despite recent advancements options, remains challenge due complexity heterogeneity CRC. emphasized need multidisciplinary approach integration emerging therapies improve patient outcomes.

Язык: Английский

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