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Cited by 1,471Liver Disease Diagnosis and TreatmentLipid metabolism and biosynthesisLiver physiology and pathology

Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease

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Ipsen, David Højland, Lykkesfeldt, Jens, Tveden-Nyborg, Pernille·2018·Cellular and Molecular Life Sciences
DOI 10.1007/s00018-018-2860-6PMC PMC6105174
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Abstract

Non-alcoholic fatty liver disease (NAFLD) is currently the world's most common liver disease, estimated to affect up to one-fourth of the population. Hallmarked by hepatic steatosis, NAFLD is associated with a multitude of detrimental effects and increased mortality. This narrative review investigates the molecular mechanisms of hepatic steatosis in NAFLD, focusing on the four major pathways contributing to lipid homeostasis in the liver. Hepatic steatosis is a consequence of lipid acquisition exceeding lipid disposal, i.e., the uptake of fatty acids and de novo lipogenesis surpassing fatty acid oxidation and export. In NAFLD, hepatic uptake and de novo lipogenesis are increased, while a compensatory enhancement of fatty acid oxidation is insufficient in normalizing lipid levels and may even promote cellular damage and disease progression by inducing oxidative stress, especially with compromised mitochondrial function and increased oxidation in peroxisomes and cytochromes. While lipid export initially increases, it plateaus and may even decrease with disease progression, sustaining the accumulation of lipids. Fueled by lipo-apoptosis, hepatic steatosis leads to systemic metabolic disarray that adversely affects multiple organs, placing abnormal lipid metabolism associated with NAFLD in close relation to many of the current life-style-related diseases.

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Cited by

Sorted by citations

Authors
Ipsen, D. H., Lykkesfeldt, J., & Tveden-Nyborg, P.
Affiliations
University of Copenhagen (DK)
ORCID
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
2018-06-23
Volume
75
Issue
18
Pages
3313-3327
ISSN
  • 1420-682X (ISSN-L)
  • 1420-9071
DOI
10.1007/s00018-018-2860-6
PMC
PMC6105174
OpenAlex
W2810629608
Cited by
1,471
References
12
Citations by year
2026: 164 · 2025: 237 · 2024: 269 · 2023: 238 · 2022: 223 · 2021: 174 · 2020: 123 · 2019: 39 · 2018: 4
FWCI
12.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Life Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
non-alcoholic fatty liver disease, hepatic steatosis, hepatic lipid accumulation, lipid homeostasis, fatty acid uptake, de novo lipogenesis, fatty acid oxidation, lipid export, oxidative stress, mitochondrial dysfunction, peroxisomal dysfunction
MeSH terms
Animals, Fatty Acids, Humans, Hypoglycemic Agents, Liver, Mitochondria, Reactive Oxygen Species, Lipid Metabolism, Fatty Acid Transport Proteins, Non-alcoholic Fatty Liver Disease

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