Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons From Animal Models

den Boer, M.; Voshol, P.J.; Kuipers, F.; Havekes, L.M.; Romijn, J.A.

doi:10.1161/01.atv.0000116217.57583.6e

Cited by 260Liver Disease Diagnosis and TreatmentDiet, Metabolism, and DiseaseDiabetes, Cardiovascular Risks, and Lipoproteins

Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons From Animal Models

den Boer, M., Voshol, P.J., Kuipers, F., Havekes, L.M., Romijn, J.A.·2004·Arteriosclerosis, Thrombosis, and Vascular Biology

DOI 10.1161/01.atv.0000116217.57583.6e

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Abstract

Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance, and type 2 diabetes mellitus. Recently, attention has been focused on the excessive accumulation of triglycerides (TG) in the liver as part of this syndrome. In this review, important principles of the pathophysiological involvement of the liver in the metabolic syndrome obtained in rodent models are summarized. We focus on non-alcoholic causes of steatosis, because the animal experiments we refer to did not include alcohol as an experimental condition. In general, there is continuous cycling and redistribution of non-oxidized fatty acids between different organs. The amount of TG in an intrinsically normal liver is not fixed but can readily be increased by nutritional, metabolic, and endocrine interactions involving TG/free fatty acid (FFA) partitioning and TG/FFA metabolism. Several lines of evidence indicate that hepatic TG accumulation is also a causative factor involved in hepatic insulin resistance. Complex interactions between endocrine, metabolic, and transcriptional pathways are involved in TG-induced hepatic insulin resistance. Therefore, the liver participates passively and actively in the metabolic derangements of the metabolic syndrome. We speculate that similar mechanisms may also be involved in human pathophysiology.

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The metabolic syndrome is an independent indicator for chronic kidney disease and may be related to liver steatosis.
“The metabolic syndrome is also an independent indicator for chronic kidney disease [636] and may be related to liver steatosis [637].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [637]
In obesity, fatty liver has frequently been linked to hepatic insulin resistance.
“Steatosis has often been associated with hepatic IR in the context of obesity [43].”
From Vasopressin and hydration play a major role in the development of glucose intolerance and hepatic steatosis in obese rats (2015) · cites this paper as [43]

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Boelsterli UA, Bedoucha M. Toxicological consequences of altered per- oxisome proliferator-activated receptor gamma (PPARgamma) expression in the liver: insights from models of obesity and type 2 diabetes. Biochem Pharmacol. 2002;63:1-10.

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Self-citation

Authors: den Boer, M., Voshol, P. J., Kuipers, F., Havekes, L. M., & Romijn, J. A.
Affiliations: From TNO Prevention and Health (M.d.B., P.J.V., L.M.H.), Gaubius Laboratory Leiden, Leiden, The Netherlands; Department of Endocrinology and Diabetes (M.d.B., P.J.V., J.A.R.), Department of General Internal Medicine (L.M.H.), and Department of Cardiology (L.M.H.), Leiden University Medical Center, Leiden, The Netherlands; and Center for Liver, Digestive, and Metabolic Diseases (F.K.), Department of Pediatrics, University Hospital Groningen, Groningen, The Netherlands.
Leiden University (NL)
ORCID: Voshol, P.J.
Kuipers, F.
Romijn, J.A.
Venue: Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2004-04
Volume: 24
Issue: 4
Pages: 644-649
ISSN: 1079-5642 (ISSN-L)
1524-4636
DOI: 10.1161/01.atv.0000116217.57583.6e
OpenAlex: W2160518844
Cited by: 260
References: 49
Citations by year: 2026: 1 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 13 · 2016: 15 · 2015: 17 · 2014: 5 · 2013: 6 · 2012: 16
FWCI: 3.67
Type: journal article
Language: en
Open access: closed
Locations: Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
TNO Repository (submittedVersion)
Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders: Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Topics: Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: hepatic steatosis, metabolic syndrome, non-alcoholic fatty liver disease, triglyceride accumulation, hepatic insulin resistance, visceral obesity, dyslipidemia, type 2 diabetes, rodent models
MeSH terms: Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Dogs, Fatty Acids, Fatty Liver, Glucose, Homeostasis, Humans, Hyperlipidemias, Insulin Resistance, Liver, Models, Biological, Obesity, Rats, Zucker, Transcription, Genetic, Triglycerides, Models, Animal, Metabolic Syndrome, Mice, Rats

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Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons From Animal Models

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