on January 8, 2004
Arteriosclerosis, Thrombosis, and Vascular Biology. 2004
Published online before print January 8, 2004, doi: 10.1161/01.ATV.0000116217.57583.6e
Published online before print January 8, 2004, doi: 10.1161/01.ATV.0000116217.57583.6e
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Submitted on September 10, 2003
Accepted on December 23, 2003
Hepatic Steatosis: A Mediator of the Metabolic Syndrome: Lessons From Animal Models
M. den Boer ;
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.
* To whom correspondence should be addressed. E-mail: lm.havekes{at}pg.tno.nl.
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.
Key words: lipoprotein metabolism • glucose metabolism • fatty acid metabolism • insulin resistance • mouse models
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