Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 13, 2022

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form NAFL, can be progressive and more susceptible to developing cirrhosis hepatocellular carcinoma. Currently, lifestyle interventions are most essential effective strategies for preventing controlling NAFL without development fibrosis. While there still limited appropriate drugs specifically treat NAFL/NASH, growing progress is being seen in elucidating pathogenesis identifying therapeutic targets. In this review, we discussed recent developments etiology prospective targets, as well pharmacological candidates pre/clinical trials patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, Importantly, evidence elucidates that disruption gut-liver axis microbe-derived metabolites drive NAFL/NASH. Extracellular vesicles (EVs) act signaling mediator, resulting accumulation, macrophage stellate cell activation, further promoting inflammation fibrosis progression during Targeting gut microbiota or EVs may serve new treatment Finally, other mechanisms, such therapy genetic approaches, also have enormous potential. Incorporating different mechanisms personalized medicine improve efficacy better benefit patients

Language: Английский

---

Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature

Current Environmental Health Reports, Journal Year: 2022, Volume and Issue: 9(4), P. 631 - 649

Published: July 28, 2022

Abstract Purpose of Review Mitochondria play various roles that are important for cell function and survival; therefore, significant mitochondrial dysfunction may have chronic consequences extend beyond the cell. already susceptible to damage, which be exacerbated by environmental exposures. Therefore, aim this review is summarize recent literature (2012–2022) looking at effects six ubiquitous classes compounds on in human populations. Recent Findings The suggests there a number biomarkers commonly used identify dysfunction, each with certain advantages limitations. Classes toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, nanomaterials can damage mitochondria varied ways, changes mtDNA copy measures oxidative most measured Other include membrane potential, calcium levels, ATP levels. Summary This identifies characterize but emerging biomarkers, cell-free blood cardiolipin provide greater insight into impacts exposures function. using novel approaches addition well-characterized ones create standardized protocols. We identified dearth studies populations exposed chemicals, nanoparticles gap knowledge needs attention.

Language: Английский

---

Pathophysiological mechanisms underlying MAFLD

Diabetes & Metabolic Syndrome Clinical Research & Reviews, Journal Year: 2020, Volume and Issue: 14(6), P. 1875 - 1887

Published: Sept. 25, 2020

Language: Английский

---

It Is High Time Physicians Thought of Natural Products for Alleviating NAFLD. Is There Sufficient Evidence to Use Them?

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(24), P. 13424 - 13424

Published: Dec. 14, 2021

Non-alcoholic fatty liver disease (NAFLD) is the most common form of all over world due to obesity pandemic; currently, therapeutic options for NAFLD are scarce, except diet recommendations and physical activity. characterized by excessive accumulation fat deposits (>5%) in with subsequent inflammation fibrosis. Studies literature show that insulin resistance (IR) may be considered as key mechanism onset progression NAFLD. Recently, using natural products an alternative approach treatment has drawn growing attention among physicians. In this review, authors present recent randomized controlled trials (RCTs) lines evidence from animal models about efficacy nutraceutics alleviating Among studied substances literature, following molecules were chosen because their presence both clinical preclinical studies: spirulina, oleuropein, garlic, berberine, resveratrol, curcumin, ginseng, glycyrrhizin, coffee, cocoa powder, epigallocatechin-3-gallate, bromelain.

Language: Английский

---

Hepatocyte Mitochondrial Dynamics and Bioenergetics in Obesity-Related Non-Alcoholic Fatty Liver Disease

Current Obesity Reports, Journal Year: 2022, Volume and Issue: 11(3), P. 126 - 143

Published: May 2, 2022

Abstract Purpose of the Review Mitochondrial dysfunction has long been proposed to play a crucial role in pathogenesis considerable number disorders, such as neurodegeneration, cancer, cardiovascular, and metabolic including obesity-related insulin resistance non-alcoholic fatty liver disease (NAFLD). Mitochondria are highly dynamic organelles that undergo functional structural adaptations meet requirements cell. Alterations nutrient availability or cellular energy needs can modify their formation through biogenesis opposite processes fission fusion, fragmentation, connection mitochondrial network areas respectively. Herein, we review discuss current literature on significance obesity dysregulation, emphasizing hepatocyte flexibility NAFLD. Recent Findings Accumulating evidence suggests involvement morphology bioenergetics dysregulations emergence NAFLD its progress steatohepatitis (NASH). Summary Most relevant data changes dynamics hold key During NAFLD, oxidative stress occurs due excessive production ROS, leading dysfunction. As result, mitochondria become incompetent uncoupled from respiratory chain activities, further promoting hepatic fat accumulation, while inflammation, resistance, disease’s deterioration. Elucidation mechanisms dysfunctional activity hepatocytes during is predominant importance for development novel therapeutic approaches towards treatment this disorder.

Language: Английский

---

Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches

Diagnostics, Journal Year: 2022, Volume and Issue: 12(2), P. 407 - 407

Published: Feb. 4, 2022

Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and its prevalence increasing globally. NAFLD a multifaceted disorder, spectrum includes steatosis to steatohepatitis, which may evolve advanced fibrosis cirrhosis. In addition, presence independently associated with higher cardiometabolic risk increased mortality rates. Considering that vast majority individuals are mainly asymptomatic, early diagnosis non-alcoholic steatohepatitis (NASH) accurate staging crucial for better stratification, monitoring targeted management patients at risk. To date, biopsy remains gold standard procedure NASH NAFLD. However, due invasive nature, research on non-invasive tests rapidly significant advances having been achieved during last decades in diagnostic field. New promising biomarkers techniques have developed, evaluated assessed, including biochemical markers, imaging modalities recent multi-omics approaches. Our article provides comprehensive review available emerging tools used assessing NAFLD, also highlighting importance validated tools.

Language: Английский

---

The Potential of the Mediterranean Diet to Improve Mitochondrial Function in Experimental Models of Obesity and Metabolic Syndrome

Nutrients, Journal Year: 2022, Volume and Issue: 14(15), P. 3112 - 3112

Published: July 28, 2022

The abnormal expansion of body fat paves the way for several metabolic abnormalities including overweight, obesity, and diabetes, which ultimately cluster under umbrella syndrome (MetS). Patients with MetS are at an increased risk cardiovascular disease, morbidity, mortality. coexistence distinct is associated release pro-inflammatory adipocytokines, as components low-to-medium grade systemic inflammation oxidative stress. Adopting healthy lifestyles, by using appropriate dietary regimens, contributes to prevention treatment MetS. Metabolic can influence function energetic capacity mitochondria, observed in many obesity-related cardio-metabolic disorders. There preclinical studies both cellular animal models, well clinical studies, dealing nutrients Mediterranean diet (MD) dysfunctional mitochondria obesity term "

Language: Английский

---

The Potential Role of Cellular Senescence in Non-Alcoholic Fatty Liver Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(2), P. 652 - 652

Published: Jan. 7, 2022

Non-alcoholic fatty liver disease (NAFLD) represents an increasing global health burden. Cellular senescence develops in response to cellular injury, leading not only cell cycle arrest but also alterations of the phenotype and metabolic functions. In this review, we critically discuss currently existing evidence for involvement NAFLD order identify areas requiring further exploration. Hepatocyte can be a central pathomechanism as it may foster intracellular fat accumulation, fibrosis inflammation, due secretion senescence-associated inflammatory mediators. However, some non-parenchymal types, such hepatic stellate cells, beneficial by reducing extracellular matrix deposition thereby fibrosis. Deciphering detailed interaction between will essential discover novel therapeutic targets halting progression.

Language: Английский

---

Mitochondrial dysfunction: A promising therapeutic target for liver diseases

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(3), P. 101115 - 101115

Published: Sept. 17, 2023

The liver is an important metabolic and detoxification organ hence demands a large amount of energy, which mainly produced by the mitochondria. Liver tissues patients with alcohol-related or non-alcohol-related diseases contain ultrastructural mitochondrial lesions, DNA damage, disturbed dynamics, compromised ATP production. Overproduction reactive oxygen species induces oxidative damage to proteins DNA, decreases membrane potential, triggers hepatocyte inflammation, promotes programmed cell death, all impair function. Mitochondrial may be potential novel non-invasive biomarker risk progression cirrhosis hepatocellular carcinoma in infected hepatitis B virus. We herein present review mechanisms dysfunction development acute injury chronic diseases, such as carcinoma, viral hepatitis, drug-induced injury, alcoholic disease, non-alcoholic fatty disease. This also discusses mitochondrion-centric therapies for treating diseases.

Language: Английский

---

Nutrients, Physical Activity, and Mitochondrial Dysfunction in the Setting of Metabolic Syndrome

Nutrients, Journal Year: 2023, Volume and Issue: 15(5), P. 1217 - 1217

Published: Feb. 28, 2023

Metabolic syndrome (MetS) is a cluster of metabolic risk factors for diabetes, coronary heart disease, non-alcoholic fatty liver and some tumors. It includes insulin resistance, visceral adiposity, hypertension, dyslipidemia. MetS primarily linked to lipotoxicity, with ectopic fat deposition from storage exhaustion, more than obesity per se. Excessive intake long-chain saturated acid sugar closely relates lipotoxicity through several pathways, including toll-like receptor 4 activation, peroxisome proliferator-activated receptor-gamma regulation (PPARγ), sphingolipids remodeling, protein kinase C activation. These mechanisms prompt mitochondrial dysfunction, which plays key role in disrupting the metabolism acids proteins developing resistance. By contrast, monounsaturated, polyunsaturated, medium-chain (low-dose) acids, as well plant-based whey protein, favors an improvement sphingolipid composition profile. Along dietary modification, regular exercises aerobic, or combined training can target improve function components. This review aimed summarize main biochemical aspects related physiopathology its implications machinery while discussing potential diet exercise counteracting this complex clustering dysfunctions.

Language: Английский

---