Induction of the apolipoprotein AI gene by fasting: A relationship with ketosis but not with ketone bodies

Apolipoprotein Al (apoAI) expression is inversely related to the incidence of atherosclerosis. ApoAI expression is also influenced by the nutritional state and diabetes. We used both cell culture and animal models to examine the effect of fasting and ketoacidosis on apoAI gene expression. Two days o f food deprivation in rats increased hepatic and intestinal apoAI mRNA by 2 .6- and 2.3-fold, respectively (P <.05). The absolute concentration of plas ma apoAI did not change. However, the plasma apoAI concentration relative t o the plasma concentration of serum proteins was increased 23% (P <.05). In fasting rats, there was a significant positive correlation between the ser um beta -hydroxybutyrate concentration and hepatic or intestinal apoAI mRNA level. Despite this correlation, changes in apoAI mRNA are probably not me diated by ketone bodies, since neither hepatic nor intestinal apoAI mRNA le vels were altered in rats maintained on a ketogenic diet for 10 days or tre ated with isobutyramide, an orally active ketone analog. In addition, the a ctivity of the rat apoAI promoter was not altered in Hep G2 cells treated w ith isobutyramide or fatty acids or exposed to hypoglycemic conditions, whi le dexamethasone increased promoter activity 1.9-fold (P <.05). These data indicate that metabolic changes other than ketone bodies, such as an increa se in plasma glucocorticoids, may account for starvation-induced expression of apoAI. Copyright (C) 2000 by W.B. Saunders Company.