Title
Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons from Animal Models
Author
den Boer, M.
Voshol, P.J.
Kuipers, F.
Havekes, L.M.
Romijn, J.A.
TNO Preventie en Gezondheid
Publication year
2004
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. Chemicals / CAS: alcohol, 64-17-5; Fatty Acids; Glucose, 50-99-7; Triglycerides
Subject
Biology
Biomedical Research
Fatty acid metabolism
Glucose metabolism
Insulin resistance
Lipoprotein metabolism
Mouse models
Alcohol
Triacylglycerol
Animal experiment
Animal model
Disease association
Dyslipidemia
Endocrine system
Genetic transcription
Glucose metabolism
Lnsulin resistance
Lipid liver level
Metabolic syndrome X
Mouse
Non insulin dependent diabetes mellitus
Nonhuman
Partition coefficient
Pathophysiology
Rodent
Short survey
Adipose Tissue
Animals
Diabetes Mellitus, Type 2
Dogs
Fatty Acids
Fatty Liver
Glucose
Homeostasis
Humans
Hyperlipidemias
Insulin Resistance
Liver
Metabolic Syndrome X
Mice
Models, Animal
Models, Biological
Obesity
Rats
Rats, Zucker
Transcription, Genetic
Triglycerides
To reference this document use:
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DOI
https://doi.org/10.1161/01.atv.0000116217.57583.6e
TNO identifier
237683
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 24 (4), 644-649
Document type
article