Response of apolipoprotein E*3-Leiden transgenic mice to dietary fatty acids: combining liver proteomics with physiological data.
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, trans10,cis12 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 beta-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.
de Roos
Baukje
B
Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK. b.deroos@rowett.ac.uk
Duivenvoorden
Ilse
I
Rucklidge
Garry
G
Reid
Martin
M
Ross
Karen
K
Lamers
Robert-Jan A N
RJ
Voshol
Peter J
PJ
Havekes
Louis M
LM
Teusink
Bas
B
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis; D001786:Blood Glucose / Q000032:analysis; D002462:Cell Membrane / Q000737:chemistry; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D003600:Cytosol / Q000737:chemistry; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005227:Fatty Acids / Q000008:administration & dosage*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D007328:Insulin / Q000097:blood; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis / Q000097:blood; D008099:Liver / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D019301:Oleic Acid / Q000008:administration & dosage; D009829:Oleic Acids; D009929:Organ Size; D011506:Proteins / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014280:Triglycerides / Q000032:analysis / Q000097:blood
D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D001786:Blood Glucose; D004041:Dietary Fats; D005227:Fatty Acids; D005395:Fish Oils; D007328:Insulin; D044243:Linoleic Acids, Conjugated; D008055:Lipids; D009829:Oleic Acids; D011506:Proteins; D014280:Triglycerides; C052720:apolipoprotein E3 (Leidein); D019301:Oleic Acid; C011459:elaidic acid; D002784:Cholesterol; D020155:3-Hydroxybutyric Acid