BACKGROUND: Although fish oil has hypolipidemic and antiatherosclerotic properties, the potential for white adipose tissue (WAT) to mediate these effects has not been studied.

DESIGN: LDL-receptor deficient (LDLR–/–) mice were fed high fat, olive oil–containing diets supplemented with additional olive oil or with fish oil for 12 wk.

RESULTS: Fish oil feeding significantly reduced plasma lipid levels. In contrast, lipid storage in WAT was increased in fish oil–fed mice as evidenced by increased total fat (P < 0.05) and perigonadal WAT mass (P < 0.05), increased cholesterol storage (P < 0.001), and adipocyte hypertrophy. Despite increased adipose tissue mass, WAT-specific inflammation and insulin sensitivity were improved (P < 0.05), concomitant with reduced macrophage infiltration. Furthermore, fish oil increased WAT and plasma levels of adiponectin. In addition, fish oil feeding decreased the formation of proinflammatory F2- isoprostanes, markers of oxidative stress (P < 0.05).

CONCLUSION: The increased WAT lipid storage in fish oil–fed mice was associated with reduced lipid accumulation in liver (P < 0.05) and decreased atherosclerotic lesion area (P < 0.05). Taken together, these data highlight the specific role of WAT in regulating dietary fish oil–mediated improvement in systemic lipid homeostasis and atherosclerosis.