How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?

Hepatology International, Journal Year: 2021, Volume and Issue: 15(1), P. 21 - 35

Published: Feb. 1, 2021

Abstract Background Non-alcoholic fatty liver disease (NAFLD), characterized as excess lipid accumulation in the which is not due to alcohol use, has emerged one of major health problems around world. The dysregulated metabolism creates a lipotoxic environment promotes development NAFLD, especially progression from simple steatosis (NAFL) non-alcoholic steatohepatitis (NASH). Purposeand Aim This review focuses on mechanisms liver, with an emphasis metabolic fate free acids (FFAs) NAFLD and presents update relevant cellular processes/mechanisms that are involved lipotoxicity. changes levels various species result imbalance between lipolysis/lipid uptake/lipogenesis oxidation/secretion can cause organellar dysfunction, e.g. ER stress, mitochondrial lysosomal JNK activation, secretion extracellular vesicles (EVs) aggravate (or be exacerbated by) hypoxia ultimately lead cell death. aim this provide overview how abnormal leads lipotoxicity context NAFLD.

Language: Английский

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Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2020, Volume and Issue: 18(1), P. 24 - 39

Published: Oct. 22, 2020

Language: Английский

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Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans

Molecular Metabolism, Journal Year: 2020, Volume and Issue: 50, P. 101122 - 101122

Published: Nov. 20, 2020

Nonalcoholic fatty liver disease (NAFLD) comprises hepatic alterations with increased lipid accumulation (steatosis) without or inflammation (nonalcoholic steatohepatitis, NASH) and/or fibrosis in the absence of other causes disease. NAFLD is developing as a burgeoning health challenge, mainly due to worldwide obesity and diabetes epidemics. This review summarizes knowledge on pathogenesis underlying by focusing studies humans hypercaloric nutrition, including effects saturated fat fructose, well adipose tissue dysfunction, leading lipotoxicity, abnormal mitochondrial function, oxidative stress, highlights intestinal dysbiosis. These mechanisms are discussed context current treatments targeting metabolic pathways results related clinical trials. Recent have provided evidence that certain conditions, for example, severe insulin-resistant (SIRD) subgroup (cluster) presence an increasing number gene variants, seem predispose excessive risk its accelerated progression. trials been frequently unsuccessful halting preventing progression, perhaps partly unselected cohorts later stages NAFLD. On basis this literature review, study proposed screening individuals highest genetic acquired SIRD subgroup, treatment concepts earliest pathophysiolgical alterations, namely, adipocyte dysfunction insulin resistance.

Language: Английский

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Mitochondrial Stasis Reveals p62-Mediated Ubiquitination in Parkin-Independent Mitophagy and Mitigates Nonalcoholic Fatty Liver Disease

Cell Metabolism, Journal Year: 2018, Volume and Issue: 28(4), P. 588 - 604.e5

Published: July 15, 2018

Language: Английский

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Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease

BMC Medicine, Journal Year: 2018, Volume and Issue: 16(1)

Published: July 31, 2018

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of worldwide. It affects an estimated 20% general population, based on cohort studies varying size and heterogeneous selection. However, prevalence incidence recorded NAFLD diagnoses in unselected real-world health-care records unknown. We harmonised health from four major European territories assessed age- sex-specific point over past decade.Data were extracted The Health Improvement Network (UK), Search Database (Italy), Information System for Research Primary Care (Spain) Integrated (Netherlands). Each database uses a different coding system. Prevalence estimates pooled across databases by random-effects meta-analysis after log-transformation.Data available 17,669,973 adults, which 176,114 had diagnosis NAFLD. Pooled trebled 0.60% 2007 (95% confidence interval: 0.41-0.79) to 1.85% (0.91-2.79) 2014. Incidence doubled 1.32 (0.83-1.82) 2.35 (1.29-3.40) per 1000 person-years. FIB-4 non-invasive estimate fibrosis could be calculated 40.6% patients, whom 29.6-35.7% indeterminate or high-risk scores.In largest primary-care record study its kind date, rates are much lower than expected suggesting under-diagnosis under-recording. Despite this, we have identified rising diagnosis. Improved recognition may identify people who will benefit risk factor modification emerging therapies prevent progression cardiometabolic hepatic complications.

Language: Английский

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Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials

Metabolites, Journal Year: 2021, Volume and Issue: 11(2), P. 73 - 73

Published: Jan. 27, 2021

To assess the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for treatment nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH), we performed a systematic review and meta-analysis randomized controlled trials (RCTs). Three large electronic databases were systematically searched (up to 15 December 2020) identify placebo-controlled active-controlled RCTs using different GLP-1 RAs. We included eleven phase-2 (involving total 936 middle-aged individuals) that used liraglutide (n = 6 RCTs), exenatide 3 dulaglutide 1 RCT) semaglutide specifically treat NAFLD NASH, detected by biopsy 2 RCTs) imaging techniques 9 RCTs). Compared placebo reference therapy, with RAs median 26 weeks was associated significant reductions in absolute percentage fat content on magnetic resonance-based (pooled weighted mean difference: -3.92%, 95% confidence intervals (CI) -6.27% -1.56%) serum enzyme levels, as well greater histological resolution NASH without worsening fibrosis random-effects odds ratio 4.06, CI 2.52-6.55; only). In conclusion, (mostly semaglutide) is promising option warrants further investigation.

Language: Английский

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Nonalcoholic fatty liver disease and Type 2 diabetes mellitus

Indian Journal of Endocrinology and Metabolism, Journal Year: 2018, Volume and Issue: 22(3), P. 421 - 421

Published: Jan. 1, 2018

Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) commonly exist together. It has been regarded as a manifestation of the metabolic syndrome. The presentations NAFLD range from simple steatosis (NAFL), steatohepatitis (NASH), cirrhosis. prevalence 70% among T2DM patients. Overweight/obesity insulin resistance (IR) have strongly linked with NAFLD. Noninvasive assessment staging are based on clinical parameters such age, sex, function test, platelet count, lipid profile, BMI, imaging modalities USG, transient elastography (TE), magnetic resonance mass spectroscopy. Such scoring systems TE useful in early detection predicting fibrosis. principle behind management involves an indirect effect through improvement IR glycemia thus is used for treatment well.

Language: Английский

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Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2022, Volume and Issue: 7(4), P. 367 - 378

Published: Jan. 12, 2022

Language: Английский

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Treatments for NAFLD: State of Art

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(5), P. 2350 - 2350

Published: Feb. 26, 2021

Non-alcoholic fatty liver disease (NAFLD) is to date the most common chronic in clinical practice and, consequently, a major health problem worldwide. It affects approximately 30% of adults general population and up 70% patients with type 2 diabetes (T2DM). Despite current knowledge epidemiology, pathogenesis, natural history NAFLD, no specific pharmacological therapies are until now approved for this strategies have been proposed manage it. They include: (a) lifestyle change order promote weight loss by diet physical activity, (b) control main cardiometabolic risk factors, (c) correction all modifiable factors leading development progression advanced forms (d) prevention hepatic extra-hepatic complications. In last decade, several potential agents widely investigated treatment NAFLD its forms—shedding some light but casting few shadows. include glucose-lowering drugs (such as pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter-2 (SGLT-2) inhibitors), antioxidants vitamin E), statins or other lipid lowering agents, bile non-bile acid farnesoid X activated (FXR) others. This narrative review discusses detail different available approaches prevent treat forms.

Language: Английский

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The Relationship Between Type 2 Diabetes, NAFLD, and Cardiovascular Risk

Current Diabetes Reports, Journal Year: 2021, Volume and Issue: 21(5)

Published: March 19, 2021

Language: Английский

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