Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content.
To examine the mechanism by which fish oil protects against fat-induced insulin resistance, we studied the effects of control, fish oil, and safflower oil diets on peroxisomal content, fatty acyl-CoA, diacylglycerol, and ceramide content in rat liver and muscle. We found that, in contrast to control and safflower oil-fed rats, fish oil feeding induced a 150% increase in the abundance of peroxisomal acyl-CoA oxidase and 3-ketoacyl-CoA thiolase in liver but lacked similar effects in muscle. This was paralleled by an almost twofold increase in hepatic peroxisome content (both P < 0.002 vs. control and safflower). These changes in the fish oil-fed rats were associated with a more than twofold lower hepatic triglyceride/diacylglycerol, as well as intramuscular triglyceride/fatty acyl-CoA, content. In conclusion, these data strongly support the hypothesis that n-3 fatty acids protect against fat-induced insulin resistance by serving as peroxisome proliferator-activated receptor-alpha ligands and thereby induce hepatic, but not intramuscular, peroxisome proliferation. In turn, an increased hepatic beta-oxidative capacity results in lower hepatic triglyceride/diacylglycerol and intramyocellular triglyceride/fatty acyl-CoA content.
Neschen
Susanne
S
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.
Moore
Irene
I
Regittnig
Werner
W
Yu
Chun Li
CL
Wang
Yanlin
Y
Pypaert
Marc
M
Petersen
Kitt Falk
KF
Shulman
Gerald I
GI
D000818:Animals; D002518:Ceramides / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D004798:Enzymes / Q000235:genetics / Q000502:physiology; D005395:Fish Oils / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008930:Mitochondria, Liver / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000378:metabolism* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012450:Safflower Oil / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D002518:Ceramides; D004075:Diglycerides; D004798:Enzymes; D005395:Fish Oils; D012333:RNA, Messenger; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D012450:Safflower Oil; D015118:Eicosapentaenoic Acid