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

Nonalcoholic fatty liver disease (NAFLD) comprises hepatic alterations with increased lipid accumulation (steatosis) without or with inflammation (nonalcoholic steatohepatitis, NASH) and/or fibrosis in the absence of other causes of liver disease. NAFLD is developing as a burgeoning health challenge...

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Veröffentlicht in:Molecular metabolism (Germany) Jg. 50; S. 101122
Hauptverfasser: Pafili, Kalliopi, Roden, Michael
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Germany Elsevier GmbH 01.08.2021
Elsevier
Schlagworte:
Adipocytes - metabolism
Clinical trials
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Disease Progression
Fatty Acids - metabolism
Fatty liver
Fibrosis
Genetic Predisposition to Disease
Genetic Variation
Humans
Inflammation
Insulin Resistance
Lipid Metabolism - drug effects
Lipotoxicity
Liver - cytology
Liver - pathology
Mitochondria - pathology
Non-alcoholic Fatty Liver Disease - drug therapy
Non-alcoholic Fatty Liver Disease - etiology
Non-alcoholic Fatty Liver Disease - metabolism
Non-alcoholic Fatty Liver Disease - pathology
Obesity - complications
Obesity - drug therapy
Obesity - metabolism
Oxidative Stress - drug effects
Polymorphism, Single Nucleotide
Review
Clinical trials
Insulin resistance
Inflammation
Fatty liver
Lipotoxicity
Fibrosis
ISSN:2212-8778, 2212-8778
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Zusammenfassung:Nonalcoholic fatty liver disease (NAFLD) comprises hepatic alterations with increased lipid accumulation (steatosis) without or with inflammation (nonalcoholic steatohepatitis, NASH) and/or fibrosis in the absence of other causes of liver disease. NAFLD is developing as a burgeoning health challenge, mainly due to the worldwide obesity and diabetes epidemics. This review summarizes the knowledge on the pathogenesis underlying NAFLD by focusing on studies in humans and on hypercaloric nutrition, including effects of saturated fat and fructose, as well as adipose tissue dysfunction, leading to hepatic lipotoxicity, abnormal mitochondrial function, and oxidative stress, and highlights intestinal dysbiosis. These mechanisms are discussed in the context of current treatments targeting metabolic pathways and the results of related clinical trials. Recent studies have provided evidence that certain conditions, for example, the severe insulin-resistant diabetes (SIRD) subgroup (cluster) and the presence of an increasing number of gene variants, seem to predispose for excessive risk of NAFLD and its accelerated progression. Recent clinical trials have been frequently unsuccessful in halting or preventing NAFLD progression, perhaps partly due to including unselected cohorts in later stages of NAFLD. On the basis of this literature review, this study proposed screening in individuals with the highest genetic or acquired risk of disease progression, for example, the SIRD subgroup, and developing treatment concepts targeting the earliest pathophysiolgical alterations, namely, adipocyte dysfunction and insulin resistance.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
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ISSN:2212-8778
2212-8778
DOI:10.1016/j.molmet.2020.101122