A lard-rich high-fat diet increases hepatic peroxisome proliferator-activated receptors in endotoxemic rats.

BACKGROUND

Diets high in saturated fatty acids activate chronic inflammation. We previously reported that, in even acute inflammation caused by lipopolysaccharide (LPS), liver injury was exacerbated in rats fed a lard-rich diet. Peroxisome proliferator-activated receptors (PPARs) are related to inflammation and are also key regulators of lipid metabolism. In this study, we examined effects of high-fat diet on liver injury and hepatic lipid metabolism during endotoxemia, measuring hepatic PPARs and other markers.

MATERIALS AND

METHODS

Male Wistar rats were fed a high-fat diet (HFD, 60 kcal% fat) or control diet (CD, 10 kcal% fat) for 4 or 12 wk, injected with LPS and sacrificed at 0, 1.5, or 6 h. Analyses included plasma aspartate transaminase (AST) and alanine transaminase (ALT) levels, messenger RNA (mRNA) and protein levels of hepatic PPARα and PPARγ, and mRNA levels of enzymes related to fatty acid oxidation and synthesis.

RESULTS

Endotoxemic rats on HFD for 12 wk, but not 4 wk, had higher mRNA and protein levels for hepatic PPARs, than did those on CD (P < 0.01-0.05). Similarly, these rats had increased mRNA expression of hepatic fatty acid oxidation- and synthesis-related enzymes (P < 0.01-0.05). Rats injected with LPS had more severe liver injury, indicated by plasma AST/ALT, if on the HFD for 12 wk, compared with for 4 wk.

CONCLUSIONS

Consumption of a lard-rich diet for 12 wk worsened liver injury and increased hepatic PPARα and PPARγ expression in endotoxemic rats.