Cholesterol reduces the effects of dihydroxy bile acids and fatty acids on water and solute transport in the human jejunum.

Abstract

A B S T R A C T Jejunal perfusion studies were performed in 16 healthy volunteers to test the hypothesis that initraluminal cholesterol can mitigate the fluid secretion induced by dihydroxy bile acids and fatty acids. Fluid secretion in the presence of 5 mM taurodeoxycholate was somewhat reduced by 4 mM mono-olein which was used for the solubilization of cholesterol. Addition of 0.8 mM cholesterol reduced fluid secretion further (P < 0.05). Fluid secretion induced by 4 mM oleic acid was changed to net absorption in a linear fashion with increasing cholesterol concentration in the perfusion solutions. 1 mM cholesterol reduced fluid secretion induced by 6 mM oleic acid (P < 0.005), but had no effect on fluiid secretion induced by 6 mM linolenic acid. Glucose absorption was generally affected in a similar manner as water transport. In vitro, 1 mM cholesterol reduced monomer activity of 6 mM oleic acid to 72.3+0.9% of control and that of linolenic acid to 81.1±1.7% ofcontrol. Although statistically significant (P < 0.001), the difference in the effects of cholesterol on monomer activities of the two fatty acids was rather small and it is unlikely that changes in monomer concentration of fatty acids and bile acids account for the protective effect of cholesterol. The in vivo observations point to a new physiological role for biliary cholesterol: the modification ofthe response ofthe small intestine to the effects of dihydroxy bile acids and fatty acids.

Regulation of 3‐hydroxy‐3‐methylglutaryl CoA reductase by analogs of cholesterol and bile acids in cultured intestinal mucosa

“…The reason for the incomplete effect of these sterols is unclear, but may be due to a rapid excretion and/or a longer half-life time of the intestinal enzyme (25). In accordance with our in vivo studies in the rabbit (26) aData are given as means (SD), ciency in cultured rnucosa fail to interfere with brush border cholesterol, most likely due to an induction of HMG-CoA reductase and/or use of intracellular reserves in order to stabilize membrane fluidity (23).…”

“…Compared to bile acids, the enhancement of reductase is less pronounced (10). Therefore, also in cultured intestine, HMG-CoA reductase activity seems to be a function of tissue cholesterol homeostatis, balancing the detergent effects of bile acids, demonstrated previously (10), and similar substances to avoid changes in fluid secretion (23) and membrane fluidity (4). This is supported by the remarkably stable brush border cholesterol (Table I), when sodium and glycofusidate concentrations were varied between 1 and 5 raM.…”

Hepatic Free Fatty Acids in Alcoholic Liver Disease and Morbid Obesity

“…On the other hand, an analysis of lipid droplets from rat livers showed no free fatty acids in the floating lipid layer (30). Other potentially mitigating factors are the binding of fatty acids to protein (31), and the presence of cholesterol (32).…”

Intestinal Secretory Mechanisms in Irritable Bowel Syndrome–Diarrhea

“…63,64 In patients with IBS-D, there is evidence that the small intestinal mucosa is more sensitive to secretory effects of BAs compared to mucosa from healthy controls. 65 Variation in GPBAR1 genotype (rs11554825, which is in strong linkage disequilibrium with mutations that alter expression and function of the receptor) 66 was significantly associated with colonic transit at 48 hours, 67 a surrogate of the intestinal secretory effects of BAs; these genotype data are consistent with a secretory diathesis in patients with IBS-D and could potentially explain the increased secretory response of ileal mucosa to infused BAs.…”