Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content

Abstract

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.

Figures

Fig. 1

Fatty acid profile (A) of soybean oil (control diet), safflower oil, and fish oil and long-chain or very long-chain fatty acyl-CoA species in liver (B) and skeletal muscle (C) from control, safflower oil-fed, and fish oil-fed rats. Approximately 200 mg of tissue were homogenized, and long-chain/very long-chain fatty acyl-CoAs were extracted. With use of a tandem mass spectrometer, fatty acyl-CoAs were ionized in negative electrospray mode. As an internal standard, C17 CoA ester was used. *P < 0.01, **P < 0.0001 vs. control; ‡P < 0.02, ‡‡P < 0.0001 vs. safflower.

Fig. 2

Acyl-CoA oxidase (AOX) and 3-ketoacyl-CoA thiolase mRNA expression in livers from control (open bars), safflower oil-fed (gray bars), and fish oil-fed (solid bars) rats. Ten micrograms of total RNA per sample were separated on a denaturing agarose gel and transferred onto nitrocellulose membranes, and transcripts were hybridized with radiolabeled cDNA probes. Quantification was performed by use of phosphoimaging, and results are expressed in relation to cytoplasmic β-actin mRNA. *P < 0.001, **P < 0.002 vs. control; ‡P < 0.0001 vs. safflower.

Fig. 3

Postembedding electron microscopy of centrilobular rat liver sections showing peroxisomes stained for catalase with alkaline 3,3’-diaminobenzidine from control (A), safflower oil-fed (B), and fish oil-fed (C) rats. P, peroxisome; M, mitochondrion; N, nucleus; *lipid droplet; ER, endoplasmic reticulum.