Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach.
Conjugated linoleic acids (CLA) affect atherogenesis, but mechanisms are not well understood. We explored how two isomers of CLA, cis9, trans11-CLA and trans10, cis12-CLA, affected lipid and glucose metabolism, as well as hepatic protein expression, in apolipoprotein E knockout mice. After 12 wk of intervention, plasma triglyceride, NEFA, and glucose concentrations were significantly higher in the trans10, cis12-CLA group, whereas plasma triglyceride, NEFA, glucose, and insulin concentrations were significantly lower in the cis9, trans11-CLA group, compared with control mice consuming linoleic acid. Proteomics identified significant up- or down-regulation of 113 liver cytosolic proteins by either CLA isomer. Principal component analysis revealed that the treatment effect of cis9, trans11-CLA was mainly explained by the up-regulation of different posttranslational forms of heat shock protein 70 kD. In contrast, the treatment effect of trans10, cis12-CLA was mainly explained by up-regulation of key enzymes in the gluconeogenic, beta-oxidation, and ketogenesic pathways. Correlation analysis again emphasized the divergent effects of both CLA isomers on different pathways, but also revealed a linkage between insulin resistance and increased levels of hepatic serotransferrin. Thus, our systems biology approach provided novel insights into the mechanisms by which individual CLA isomers differentially affect pathways related to atherogenesis, such as insulin resistance and inflammation.
de Roos
B
B
Rowett Research Institute, Aberdeen, UK. b.deroos@rowett.ac.uk
Rucklidge
G
G
Reid
M
M
Ross
K
K
Duncan
G
G
Navarro
M A
MA
Arbones-Mainar
J M
JM
Guzman-Garcia
M A
MA
Osada
J
J
Browne
J
J
Loscher
C E
CE
Roche
H M
HM
D000821:Animal Feed; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001823:Body Composition; D001835:Body Weight; D003600:Cytosol / Q000378:metabolism; D004032:Diet; D005227:Fatty Acids / Q000378:metabolism; D008040:Genetic Linkage; D005947:Glucose / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D019787:Linoleic Acid / Q000737:chemistry*; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D025341:Principal Component Analysis; D040901:Proteomics / Q000379:methods*; D049490:Systems Biology; D014280:Triglycerides / Q000378:metabolism
D001057:Apolipoproteins E; D001786:Blood Glucose; D005227:Fatty Acids; D018840:HSP70 Heat-Shock Proteins; D007328:Insulin; D044243:Linoleic Acids, Conjugated; D014280:Triglycerides; C503589:cis-9, trans-11-conjugated linoleic acid; C496197:trans-10,cis-12-conjugated linoleic acid; D019787:Linoleic Acid; D005947:Glucose; D010100:Oxygen