Dietary interventions with
fish oil have been found to protect against the development of high-fat diet-induced
insulin resistance and to decrease the expression of
tumor necrosis factor (
TNF)-alpha. However, the effect of
fish oil administration on preexisting
insulin resistance is subject to debate. In the present study, we examined the mechanism by which
fish oil affects preexisting
insulin resistance. High fat diet-induced
insulin-resistant
ApoE*3-Leiden transgenic mice were treated for 10 wk as follows: 1) high fat diet (control group), 2) high fat diet with 3 g/100 g
fish oil and 3) high fat diet but food intake restricted to 75% of the ad libitum food intake. We measured plasma
glucose,
insulin,
free fatty acids (FFA) and
triglyceride (TG) levels throughout the study. After the 10-wk dietary intervention period we performed hyperinsulinemic euglycemic analyses and measured
insulin sensitivity and FFA turnover. Furthermore, we then determined the VLDL-TG production rate and
TNF-alpha protein expression in white adipose tissue (WAT). Compared with control mice, the
insulin sensitivity of mice treated with
fish oil was not affected, whereas it was improved (P < 0.05) for energy-restricted mice. FFA turnover was unaffected in both
fish oil-treated and energy-restricted mice. Compared with controls, hepatic VLDL-TG production was lower (P < 0.05) with
fish oil feeding but greater with energy restriction (P < 0.05). Interestingly, the level of
TNF-alpha protein in WAT was lower (P < 0.05) in both groups. We conclude that partial replacement of saturated fat by
fish oil does not improve preexisting high fat diet-induced
insulin resistance, although it lowers
TNF-alpha protein levels in WAT.