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Am J Physiol Endocrinol Metab (October 23, 2001). doi:10.1152/ajpendo.00414.2001
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Articles in PresS, published online ahead of print October 22, 2001
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00414.2001
Submitted on September 18, 2001
Accepted on October 16, 2001

Contrasting Effects of Fish oil and Safflower Oil on Hepatic Peroxisomal and Tissue Lipid Content

Susanne Neschen1, Irene Moore1, Werner Regittnig1, Chun Li Yu1, Yanlin Wang1, Marc Pypaert1, Kitt F Petersen1, and Gerald I Shulman2*

1 Medicine, Yale University, New Haven, CT, USA
2 Medicine, Yale University, New Haven, CT, USA; Howard Hughes Medical Institute, New Haven, CT, USA

* To whom correspondence should be addressed. E-mail: gerald.shulman{at}yale.edu.

In order 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 serving as PPAR{alpha} ligands and thereby inducing hepatic, but not intramuscular, peroxisome proliferation. In turn, an increased hepatic ß-oxidative capacity results in lower hepatic triglyceride/diacylglycerol and intramyocellular triglyceride/fatty acyl CoA content.




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