Effects of dexamethasone and linoleic acid on hepatic secretion of biliarylipids and anionic polypeptide factor: In vivo and in vitro studies

Synthetic glucocorticoids, such as dexamethasone, and diets enriched with u nsaturated fatty acids have been shown to stimulate hepatic bile salt synth esis. This fact led us to investigate the effects of dexamethasone and lino leic acid supplementation on bile secretion. Cholesterol (Ch) and phospholi pid secretions are bile acid dependent. Ch and phospholipid in bile are als o highly bound to a small apoprotein, the anionic polypeptide factor (APF). In bile, APF may play a physiological role in stabilizing cholesterol:phos pholipid vesicles and might also be important in the regulatory process of bile lipid secretion. In order to study the factors influencing bile secret ion, the biliary secretion rates of bile lipids and APF were experimentally modulated in perfused rat liver (PRL) and HepG2 cells. As expected, dexame thasone induced an increase in the biliary secretion rate of bile salts (BS )in the two models (PRL: 34 up to 67 nmol/l/ min/g liver; HepG2 cells: 234% vs. 100% in controls). The bile secretion rates for phospholipids (PRL: fr om 5 down to 1.5 nmol/l/min/g liver; HepG2 cells: 93 vs. 100% in controls) and APF (PRL: from 0.34 down to 0.12 mu g/l/min/g liver; cells: 86 vs. 100% in controls) rapidly decreased independently from those of BS. The data fr om experimental cell models supplemented with linoleic acid indicated a cor relation between the BS and APF levels (APF: 71 and 63%; BS: 161 and 197% v s. 100% in controls). The phospholipid level was regulated independently fr om that of APF and BS and increased (106 and 111% vs. 100% in controls), wh ile Ch remained nevertheless unchanged. Our data showed that dexamethasone induced changes in bile and that linoleic acid clearly impaired the regulat ion exerted by the dexamethasone on bile lipids.