The DOI matches its Crossref record; 239 of the 244 references it cites were found in a registry or an index.
Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans
Open accessAbstract
BACKGROUND: 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. SCOPE OF REVIEW: 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. MAJOR CONCLUSIONS: 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.
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“As a consequence, adipose tissue insulin resistance develops, paralleled by altered adipokine (i.e., adiponectin, leptin) secretion and impaired mitochondrial function, further promoting adipose tissue inflammation [19,20].”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [19]
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“Here, NEFA promote hepatic triglyceride storage and gluconeogenesis [26], when the capacity of the liver to oxidize these substrates or export them as very-low-density lipoproteins (VLDL) is depleted [19].”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [19]
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Metadata
- Authors
- Pafili, K., & Roden, M.
- Affiliations
- Deutsches Diabetes-Zentrum e.V. (DE)
- Corresponding author
- Roden, Michael
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 50
- Pages
- 101122
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC8324683
- OpenAlex
- W3104053913
- Cited by
- 330
- References
- 244
- Citations by year
- 2026: 47 · 2025: 63 · 2024: 85 · 2023: 73 · 2022: 40 · 2021: 19
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministry of Innovation, Science, Research and Technology of the State of North Rhine-Westphalia
- Deutsche Forschungsgemeinschaft (CRC 1116/2)
- Bundesministerium für Bildung und Forschung
- Bundesministerium für Gesundheit
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatic steatosis, liver fibrosis, saturated fat, fructose, adipose tissue dysfunction, hepatic lipotoxicity, mitochondrial dysfunction, oxidative stress, gut dysbiosis, severe insulin-resistant diabetes, genetic risk variants, NAFLD progression, NAFLD screening, insulin resistance, NAFLD treatment
- MeSH terms
- Diabetes Mellitus, Type 2, Fatty Acids, Humans, Insulin Resistance, Liver, Mitochondria, Obesity, Genetic Variation, Adipocytes, Oxidative Stress, Disease Progression, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Lipid Metabolism, Non-alcoholic Fatty Liver Disease
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