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-α ligands and thereby induce hepatic, but not intramuscular, peroxisome proliferation. In turn, an increased hepatic β-oxidative capacity results in lower hepatic triglyceride/diacylglycerol and intramyocellular triglyceride/fatty acyl-CoA content.

Skeletal muscle lipid metabolism with obesity

“…Long-chain fatty acyl-CoAs were extracted from the muscle sample by solid-phase extraction, and 17-carbon CoA was added as an internal standard, as previously described (2,27). A tandem mass spectrometer API 3000 (Perkin-Elmer Sciex) interfaced with a TurboIonspray ionization source was used for MS-MS analysis (27). Fatty acyl-CoAs were ionized in a negative electrospray mode, and the transition pairs [M-2 H] 2Ϫ /[M-H-80] Ϫ were monitored in multiple reaction monitoring mode.…”

“…Fatty acyl-CoAs were ionized in a negative electrospray mode, and the transition pairs [M-2 H] 2Ϫ /[M-H-80] Ϫ were monitored in multiple reaction monitoring mode. Doubly charged ions and corresponding product ions (precursor minus phosphate group) were chosen as a transition pair for multiple-reactions monitoring for quantitation (27). Total long-chain fatty acyl-CoA content was calculated as the sum of the long-chain fatty acyl-CoA species measured.…”

n-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity?

“…The following mechanisms are likely to be implicated: (a) the decrease in muscle triglyceride content. Indeed, it has been shown that insulin sensitivity is related to muscle triglycerides in rats fed a high fat diet and that muscle triglyceride content is decreased by fish oil [34,35]; (b) the decrease in LCFACoA as demonstrated by Neschen et al [36]; (c) the decrease in visceral fat mass [37]; (d) the increase in unsaturation of membrane phospholipids. A strong positive relationship has been shown between the insulin sensitivity of rat muscles and the degree of unsaturation of muscle membrane phospholipids [32].…”

“…In rats fed a high fat diet, substitution for fish oil in the diet reduces liver triglyceride content [35,36]. n-3 PUFA exert their effects by coordinately suppressing lipogenesis and upregulating fatty acid oxidation.…”

Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins

“…These data raise the question of whether acquired obesity indeed regulates liver fat content. Alternative regulators would be genetic factors and acquired factors other than obesity, such as dietary fat content and composition (24,44).…”