EFFECTS OF A FISH-OIL LARD DIET ON RAT PLASMA-LIPOPROTEINS, LIVER FAS, AND LIPOLYTIC ENZYMES

The effects of a fish oil concentrate on blood lipids and lipoproteins were examined in relation to their effects on liver fatty acid synthase (FAS), 3-hydroxy-3methylglutaryl-CoA (HMG-CoA) reductase, adipose tissue lipoprotein lipase (LPL), and hepatic triglyceride lipase (H-TGL). For 15 days, a-mo-old rats were fed a control diet (10% of calories from fat, 4% fat by weight) or diets with 50% of calories (25% wt/wt) provided by lard, lard and fish oil concentrate (35%/15%), or lard and corn oil (35%/15%). The high-lard diet increased plasma chylomicron and liver triglycerides. The high-lard diet greatly decreased FAS, HMG-CoA reductase, and LPL activities; it also reduced H-TGL activity. Compared with the lard diet, the lard-fish oil diet decreased plasma TG by drastically lowering chylomicron (4-fold, P < 0.001) and very-low-density lipoprotein levels(P < 0.001). It also reduced high-density lipoprotein levels. The lard-fish oil diet prevented hepatic triglyceride accumulation and decreased FAS activity and mass by 3.5-fold (P < 0.001) but did not further decrease HMG-CoA reductase activity. Adipose tissue LPL activity was 2.5-fold (P < 0.001) higher with the lard-fish oil diet than with the lard diet, and H-TGL activity decreased significantly (-32%, P < 0.01), despite unaltered levels of H-TGL mRNA. These effects were significant with only 10% fish oil concentrate in the lard diet. They were not observed viith the lard-corn oil diet. Thus inclusion of fish oil concentrate in a lard diet results in a marked decrease in plasma chylomicron and very-low-density lipoprotein levels associated with an almost total suppression of hepatic FAS and a sustained adipose tissue LPL activity. The decreased H-TGL activity may be a secondary adaptation to the induced hypolipidemia or may result from a specific posttranscriptional inhibition of H-TGL gene expression by fish oil n-3 fatty acids.