Mechanisms of Disease: pathogenesis of nonalcoholic fatty liver disease
Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome. The metabolic syndrome is characterized by insulin resistance, which is produced by a complex interaction between genetic factors, macronutrient intake and lifestyle that alters the cytokine profile, cell biology and biochemical milieu of the liver, adipose tissue and striated muscle. The resultant disequilibrium in lipid homeostasis causes triglycerides to accumulate in the liver. An increase in oxidative stress, due to the generation of reactive oxygen species as a result of mitochondrial abnormalities and induction of the cytochrome P-450 system could be one mechanism by which the nonalcoholic fatty liver develops into nonalcoholic steatohepatitis. The pathogenesis of cytologic ballooning and Mallory body formation and their role in NAFLD remain to be defined. In addition, inflammation and fibrosis are likely to be secondary to hepatocyte injury and death.
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In NAFL, the deposition of free fatty acids and triglycerides is caused by an increase in fatty acid uptake, lipogenesis and a concomitant decrease in VLDL-TG secretion.
“In NAFL, the deposition of free fatty acids (FFAs) and triglycerides (TGs) are caused by an increase in fatty acid uptake, lipogenesis and a concomitant decrease in VLDL-TG secretion [5].”
From Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells (2021) · cites this paper as [5]
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References 49 · Cited by 216
- Authors
- Sanyal, A. J.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Sanyal, Arun J
- ORCID
- Sanyal, Arun J
- Venue
- Nature Clinical Practice Gastroenterology & Hepatology
- Published
- 2005-01
- Volume
- 2
- Issue
- 1
- Pages
- 46-53
- ISSN
- 1743-4378 (ISSN-L)
- 1743-4386
- OpenAlex
- W1968354167
- Cited by
- 216
- References
- 49
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 12 · 2018: 14 · 2017: 14 · 2016: 7 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 10
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Clinical Practice Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, pathogenesis, insulin resistance, metabolic syndrome, hepatic lipid homeostasis, hepatic steatosis, oxidative stress, reactive oxygen species, mitochondrial dysfunction, cytochrome P450, Mallory bodies, liver inflammation, liver fibrosis, hepatocyte injury
- MeSH terms
- Cytochrome P-450 Enzyme System, Fatty Liver, Humans, Risk Factors, Triglycerides, Oxidative Stress, Disease Progression, Hepatocytes, Metabolic Syndrome, Lipid Metabolism
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