Induction of the apolipoprotein AI gene by fasting: a relationship with ketosis but not with ketone bodies.
Apolipoprotein AI (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 of food deprivation in rats increased hepatic and intestinal apoAI mRNA by 2.6- and 2.3-fold, respectively (P < .05). The absolute concentration of plasma apoAI did not change. However, the plasma apoAI concentration relative to the plasma concentration of serum proteins was increased 23% (P < .05). In fasting rats, there was a significant positive correlation between the serum beta-hydroxybutyrate concentration and hepatic or intestinal apoAI mRNA level. Despite this correlation, changes in apoAI mRNA are probably not mediated by ketone bodies, since neither hepatic nor intestinal apoAI mRNA levels were altered in rats maintained on a ketogenic diet for 10 days or treated with isobutyramide, an orally active ketone analog. In addition, the activity of the rat apoAI promoter was not altered in Hep G2 cells treated with isobutyramide or fatty acids or exposed to hypoglycemic conditions, while dexamethasone increased promoter activity 1.9-fold (P < .05). These data indicate that metabolic changes other than ketone bodies, such as an increase in plasma glucocorticoids, may account for starvation-induced expression of apoAI.
Haas
M J
MJ
Department of Internal Medicine, Saint Louis University Medical School, MO 63104, USA.
Reinacher
D
D
Pun
K
K
Wong
N C
NC
Mooradian
A D
AD
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005215:Fasting / Q000502:physiology*; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D007662:Ketosis / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000378:metabolism; D008297:Male; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D016632:Apolipoprotein A-I; D007657:Ketone Bodies; D012333:RNA, Messenger; D020155:3-Hydroxybutyric Acid