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Response of apolipoprotein E*3‐Leiden transgenic mice to dietary fatty acids: combining liver proteomics with physiological data
Author(s) -
de Roos Baukje,
Duivenvoorden Ilse,
Rucklidge Garry,
Reid Martin,
Ross Karen,
Lamers RobertJan A. N.,
Voshol Peter J.,
Havekes Louis M.,
Teusink Bas
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2974fje
Subject(s) - elaidic acid , chemistry , lipid metabolism , biochemistry , cholesterol , metabolism , fatty acid , medicine , endocrinology , biology , linoleic acid
Dietary fatty acids have a profound impact on atherosclerosis, but mechanisms are not fully understood. We studied the effects of a saturated fat diet supplemented with fish oil, trans 10, cis 12 conjugated linoleic acid (CLA), or elaidic acid on lipid and glucose metabolism and liver protein levels of APOE*3 Leiden transgenic mice, a model for lipid metabolism and atherosclerosis. Fish oil lowered plasma and liver cholesterol and triglycerides, plasma free fatty acids, and glucose but increased plasma insulin. CLA lowered plasma cholesterol but increased plasma and liver triglycerides, plasma β‐hydroxybutyrate, and insulin. Elaidic acid lowered plasma and liver cholesterol. Proteomics identified significant regulation of 65 cytosolic and 8‐membrane proteins. Many of these proteins were related to lipid and glucose metabolism, and to oxidative stress. Principal component analysis revealed that fish oil had a major impact on cytosolic proteins, and elaidic acid on membrane proteins. Correlation analysis between physiological and protein data revealed novel clusters of correlated variables, among which a metabolic syndrome cluster. The combination of proteomics and physiology gave new insights in mechanisms by which these dietary fatty acids regulate lipid metabolism and related pathways, for example, by altering protein levels of long‐chain acyl‐CoA thioester hydrolase and adipophilin in the liver.