The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(12), P. 764 - 783

Published: Aug. 15, 2023

Language: Английский

An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD)

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(6), P. 1178 - 1196

Published: June 12, 2024

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty disease, encompasses steatosis and metabolic steatohepatitis (MASH), leading to cirrhosis hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human yet be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, histopathology, transcriptome benchmarked against humans) of murine models (mostly male) ranked them using an unbiased ‘human proximity score’ define their relevance ability induce MASH-fibrosis. Here, we show Western diets align closely with MASH; high cholesterol content, extended study duration and/or genetic manipulation disease-promoting pathways are required intensify damage accelerate significant (F2+) fibrosis development. Choline-deficient rapidly MASH-fibrosis while showing relatively poor translatability. Our ranking commonly used models, based on MASLD, helps selection appropriate vivo preclinical research.

Language: Английский

Role of Insulin Resistance in the Development of Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: From Bench to Patient Care

Diabetes Spectrum, Journal Year: 2024, Volume and Issue: 37(1), P. 20 - 28

Published: Feb. 1, 2024

Insulin resistance is implicated in both the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and its progression from steatosis to steatohepatitis, cirrhosis, even hepatocellular carcinoma, which known be more common people with type 2 diabetes. This article reviews role insulin metabolic dysfunction observed obesity, diabetes, atherogenic dyslipidemia, hypertension how it a driver natural history NAFLD by promoting glucotoxicity lipotoxicity. The authors also review genetic environmental factors that stimulate steatohepatitis fibrosis their relationship cardiovascular summarize guidelines supporting treatment diabetes medications reduce resistance, such as pioglitazone or glucagon-like peptide 1 receptor agonists.

Language: Английский

SCD1 is the critical signaling hub to mediate metabolic diseases: Mechanism and the development of its inhibitors

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 115586 - 115586

Published: Dec. 1, 2023

Metabolic diseases, featured with dysregulated energy homeostasis, have become major global health challenges. Patients metabolic diseases high probability to manifest multiple complications in lipid metabolism, e.g. obesity, insulin resistance and fatty liver. Therefore, targeting the hub genes metabolism may systemically ameliorate along complications. Stearoyl-CoA desaturase 1(SCD1) is a key enzyme that desaturates saturated acids (SFAs) derived from de novo lipogenesis or diet generate monounsaturated (MUFAs). SCD1 maintains tissue homeostasis by responding to, integrating layers of endogenous stimuli, which mediated synthesized MUFAs. It critically regulates myriad physiological processes, including development, autophagy, tumorigenesis inflammation. Aberrant transcriptional epigenetic activation AMPK/ACC, SIRT1/PGC1α, NcDase/Wnt, etc, causes aberrant accumulation, thereby promoting progression non-alcoholic liver, diabetes cancer. This review assesses integrative mechanisms (patho)physiological functions inflammation autophagy. For translational perspective, potent inhibitors been developed treat various types We thus discuss multidisciplinary advances greatly accelerate development new inhibitors. In conclusion, besides cancer treatment, serve as promising target combat simultaneously.

Language: Английский

Adipokines regulate the development and progression of MASLD through organellar oxidative stress

Hepatology Communications, Journal Year: 2025, Volume and Issue: 9(2)

Published: Jan. 29, 2025

The prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), which is increasingly being recognized as a leading cause chronic pathology globally, increasing. pathophysiological underpinnings its progression, currently under active investigation, involve oxidative stress. Human adipose tissue, an integral endocrine organ, secretes array adipokines that are modulated by dietary patterns and lifestyle choices. These intricately orchestrate regulatory pathways impact glucose lipid metabolism, stress, mitochondrial function, thereby influencing the evolution hepatic steatosis progression to steatohepatitis (MASH). This review examines recent data, underscoring critical interplay reactive oxygen species, redox signaling in adipokine-mediated mechanisms. role various regulating onset MASLD/MASH through dysfunction endoplasmic reticulum stress underlying mechanisms discussed. Due emerging correlation between development MASLD positions, these potential targets for innovative therapeutic interventions management. A comprehensive understanding pathogenesis instrumental identifying therapies MASH.

Language: Английский

Liver diseases: epidemiology, causes, trends and predictions

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 4, 2025

Abstract As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles metabolism, detoxification, immune response. Various factors including viruses, alcohol, metabolites, toxins, other pathogenic agents can compromise function, leading to acute or chronic injury that may progress end-stage diseases. While sharing common features, diseases exhibit distinct pathophysiological, clinical, therapeutic profiles. Currently, contribute approximately 2 million deaths globally each year, imposing significant economic social burdens worldwide. However, there no cure for many kinds of diseases, partly due lack thorough understanding development these Therefore, this review provides comprehensive examination epidemiology characteristics covering spectrum from conditions manifestations. We also highlight multifaceted mechanisms underlying initiation progression spanning molecular cellular levels networks. Additionally, offers updates on innovative diagnostic techniques, current treatments, potential targets presently under clinical evaluation. Recent advances pathogenesis hold critical implications translational value novel strategies.

Language: Английский

Gastrointestinal cancers in lean individuals with non‐alcoholic fatty liver disease: A systematic review and meta‐analysis

Liver International, Journal Year: 2023, Volume and Issue: 44(1), P. 6 - 14

Published: Oct. 13, 2023

Abstract Background & Aims Obesity and non‐alcoholic fatty liver disease (NAFLD) are known risk factors for gastrointestinal (GI) cancers. However, GI carcinogenesis in lean NAFLD patients remains unclear. This systematic review meta‐analysis aims to investigate the association between cancer risk. Methods PubMed, Embase Cochrane Library databases were systematically searched (from inception date April 2023) cohort studies assessing cancers (body mass index [BMI] < 25 kg/m 2 or 23 Asians) non‐lean (BMI ≥25 ≥ individuals. Data from eligible extracted, was carried out using a random effects model obtain ratios (RRs) with 95% confidence intervals (CIs). Subgroup analyses, meta‐regressions sensitivity analyses also performed. study registered PROSPERO (CRD42023420902). Results Eight 56,745 individuals (11% lean) 704 cases of incident included. Lean associated higher hepatic (RR 1.77, CI 1.15–2.73), pancreatic 1.97, 1.01–3.86) colorectal 1.53, 1.12–2.09), compared NAFLD. No significant differences observed oesophagus, gastric, biliary small intestine Conclusions shows that have an increased liver, patients, emphasizing need explore tailored prevention strategies this specific patient group. Further research is required mechanisms underlying

Language: Английский

Cdo1-Camkk2-AMPK axis confers the protective effects of exercise against NAFLD in mice

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 18, 2023

Exercise is an effective non-pharmacological strategy for ameliorating nonalcoholic fatty liver disease (NAFLD), but the underlying mechanism needs further investigation. Cysteine dioxygenase type 1 (Cdo1) a key enzyme cysteine catabolism that enriched in liver, whose role NAFLD remains poorly understood. Here, we show exercise induces expression of hepatic Cdo1 via cAMP/PKA/CREB signaling pathway. Hepatocyte-specific knockout (Cdo1LKO) decreases basal metabolic rate mice and impairs effect against NAFLD, whereas hepatocyte-specific overexpression (Cdo1LTG) increases synergizes with to ameliorate NAFLD. Mechanistically, tethers Camkk2 AMPK by interacting both them, thereby activating signaling. This promotes acid oxidation mitochondrial biogenesis hepatocytes attenuate hepatosteatosis. Therefore, promoting Camkk2-AMPK pathway, acts as important downstream effector combat

Language: Английский

Unraveling Adipose Tissue Dysfunction: Molecular Mechanisms, Novel Biomarkers, and Therapeutic Targets for Liver Fat Deposition

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 380 - 380

Published: Feb. 22, 2024

Adipose tissue (AT), once considered a mere fat storage organ, is now recognized as dynamic and complex entity crucial for regulating human physiology, including metabolic processes, energy balance, immune responses. It comprises mainly two types: white adipose (WAT) brown (BAT) thermogenesis, with beige adipocytes demonstrating the plasticity of these cells. WAT, beyond lipid storage, involved in various activities, notably lipogenesis lipolysis, critical maintaining homeostasis. also functions an endocrine secreting adipokines that influence metabolic, inflammatory, processes. However, dysfunction especially related to obesity, leads disturbances, inability properly store excess lipids, resulting ectopic deposition organs like liver, contributing non-alcoholic fatty liver disease (NAFLD). This narrative review delves into multifaceted roles its composition, functions, pathophysiology WAT dysfunction. explores diagnostic approaches adipose-related disorders, emphasizing importance accurately assessing AT distribution understanding relationships between compartments health. Furthermore, it discusses therapeutic strategies, innovative therapeutics adipose-derived mesenchymal stem cells (ADMSCs)-based treatments gene therapy, highlighting potential precision medicine targeting obesity associated complications.

Language: Английский

Role of lifestyle and glucagon‐like peptide‐1 receptor agonists for weight loss in obesity, type 2 diabetes and steatotic liver diseases

Alimentary Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 59(S1)

Published: May 30, 2024

Summary Background The current obesity pandemic has given rise to associated comorbidities and complications, including type 2 diabetes metabolic dysfunction‐associated steatotic liver disease (MASLD). During the last decade, certain glucagon‐like peptide 1 receptor agonists (GLP‐1RA), originally developed as antihyperglycemic drugs, also demonstrated efficacy for weight loss. Aims To review shared pathophysiologic features of common diseases compare therapeutic strategies reduce body related complications. Methods We performed an extensive literature research describe effects lifestyle modification, first‐generation anti‐obesity GLP‐1RA on loss in humans with obesity, MASLD. Results Until recently, treatment been limited which offer moderate degree sustainability few approved drugs are either short term use or forms obesity. Some significantly decrease caloric intake weight. Liraglutide semaglutide have therefore treating people They lead a reduction hepatic fat content inflammation biopsy‐confirmed Possible limitations comprise adverse effects, adherence persistence. Conclusion Certain superior modification inducing markedly changed portfolio additional beneficial disease.

Language: Английский