The effect of diet on the expression of lecithin:cholesterol acyltransferase (LCAT) gene, the key cholesterol esterifying enzyme in plasma, is under active investigation. We observe a 2.5-fold abundance of LCAT mRNA when primary rat hepatocytes are cultured with oleic acid, in vitro. To determine if this occurs in vivo, the effect of diets rich in specific fatty acids on LCAT gene expression was investigated. Male Sprague-Dawley rats were assigned to four treatment groups and were fed either the Control diet (AIN 93M), or a similar diet supplemented with purified fats (15% w/w) containing triolein (91.4%), tripalmitin (98%) and menhaden oil for 2 weeks. Serum LCAT activity (measured with an exogenous substrate), hepatic LCAT mRNA induction (determined by Northern analyses), and lipid levels were determined after two weeks on the respective diets. Animals fed the triolein diet had significantly higher levels of circulating LCAT (33±4 vs 23±3 nMol/ml/hr for Control). Menhaden oil and tripalmitin diets, on the other hand, showed no significant influence on LCAT activity. Analyses of total RNA extracted from the livers of fed animals also indicated that diets rich in triolein stimulate the induction of hepatic LCAT mRNA by 183% above control, while menhaden oil (82%) or tripalmitin (120%) had no effect. These results suggest that oleic acid is a potent stimulator of LCAT in vitro and in vivo, and that diet or dietary components modulate LCAT gene expression.
|State||Published - 1997|