Cited by 1,077Liver Disease Diagnosis and TreatmentDiet, Metabolism, and DiseaseAlcohol Consumption and Health Effects

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Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites†

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Neuschwander‐Tetri, Brent A.·2010·Hepatology

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Abstract

A significant body of evidence now forces us to rethink the causes of NASH. Once thought to be a disease caused by triglyceride accumulation in hepatocytes with subsequent oxidant stress and lipid peroxidation causing inflammation and fibrosis, new data from animal studies and a limited number of human studies now provide convincing evidence that triglyceride accumulation does not cause insulin resistance or cellular injury in the liver. The lipotoxic liver injury hypothesis for the pathogenesis of NASH suggests that we need to focus our therapeutic efforts on reducing the burden of fatty acids going to the liver or being synthesized in the liver. This can be accomplished by improving insulin sensitivity at the level of adipose tissue to prevent inappropriate peripheral lipolysis and by preventing unnecessary de novo lipogenesis in the liver. Excess carbohydrates are the major substrates for de novo lipogenesis, and thus, reducing carbohydrate consumption through dietary changes and increasing muscle glucose uptake through exercise remain important cornerstones of treatment and prevention of lipotoxic liver injury, a disease hitherto called NASH.

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Authors: Neuschwander‐Tetri, B. A.
Affiliations: Saint Louis University (US)
Corresponding author: Neuschwander‐Tetri, Brent A.
ORCID: Neuschwander‐Tetri, Brent A.
Venue: Hepatology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2010-08
Volume: 52
Issue: 2
Pages: 774-788
ISSN: 0270-9139 (ISSN-L)
DOI: 10.1002/hep.23719
OpenAlex: W2107943478
Cited by: 1,077
References: 196
Citations by year: 2026: 29 · 2025: 61 · 2024: 66 · 2023: 78 · 2022: 75 · 2021: 86 · 2020: 106 · 2019: 72 · 2018: 66 · 2017: 72 · 2016: 77 · 2015: 60 · 2014: 64 · 2013: 52 · 2012: 47
FWCI: 5.87
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1857 d)
Locations: Hepatology (publishedVersion)
PubMed (publishedVersion)
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: nonalcoholic steatohepatitis, hepatic lipotoxicity, NASH pathogenesis, triglyceride accumulation, insulin resistance, de novo lipogenesis, adipose tissue insulin sensitivity, lipolysis, carbohydrate intake, physical activity, muscle glucose uptake
MeSH terms: Fatty Acids, Fatty Liver, Humans, Insulin Resistance, Liver, Causality, Oxidative Stress, Lipid Metabolism

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Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites†

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