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

The Effect of Select Nutrients on Serum High-Density Lipoprotein Cholesterol and Apolipoprotein A-I Levels

“…The ketoacidosis-associated down-regulation of apo A-I gene could be correlated with the process of ketogenesis but not with the presence of ketone bodies (95). In HepG2 cells, as well as in Caco2 intestinal cells, ketones and their analogs, such as butyrate or isobutyramide, do not significantly alter apo A-I expression (96). In contrast, either acidification of the culture media or altering intracellular pH with specific ionophores and inhibitors consistently suppressed apo A-I promoter activity and apo A-I production (97).…”

“…The effect of acidosis on apo A-I promoter activity occurs through a pH-responsive element (pH-RE) located within the promoter (97). Acidosis increases the specific DNA binding activity of a putative repressor protein, and the response element is either close to or overlaps a negative thyroid hormone response element that is located 3Ј and adjacent to and overlaps the apo A-I TATA element (96,97). This region also contains binding sites for other transcription factors (Fig.…”

Transcriptional Control of Apolipoprotein A-I Gene Expression in Diabetes

“…This change could be correlated with the process of ketogenesis but not with ketone bodies (23). In cell culture studies with hepatocytes and intestinal cells, ketones and their analogs such as butyrate or isobutyramide do not significantly alter apo A-I expression (24). In contrast, acidosis, induced either by changes in the pH of the culture media or by treatment with agents known to alter intracellular pH, consistently suppresses apo A-I promoter activity and apo A-I production (25).…”

“…However, not all models of ketosis show repression. For example, apo A-I mRNA and protein levels are elevated in rats placed on a high-fat ketogenic diet (24). This indicates that acidosis is a required element of apo A-I gene suppression by ketoacidosis.…”

Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4α, and PGC-1α

“…It is possible that apoA-IV gene activity is induced by an environmental stimulus (such as glucose or ketogenic products) that is required for the actions of HNF-4a and PGC-1a on the promoter. Studies of the complex regulation of the apoA-I gene have demonstrated that induction by prolonged fasting is correlated with increases in ketone bodies (52). In addition, the apoA-I gene has also been found to be responsive to glucocorticoid levels through an indirect mechanism thought to involve an in- Real-time quantitative PCR analysis of hepatic mRNA expression of PGC-1a and HNF-4a after 0, 6, 12, and 24 h fasts and 24 h fast followed by a 24 h refeed (A), apoA-IV, HNF-4a, and PGC-1a in fed or 24 h fasted HNF-4a 2/2 mice and floxed controls (B), and HNF4a and PGC-1a in adrenalectomized (Adx) and sham-operated mice (fed or fasted for 24 h) (C).…”