TY - JOUR

T1 - Inhibition of cholesterol transport in an intestine cell model by pine-derived phytosterols

AU - Yi, Jinsoo

AU - Knudsen, Tine A.

AU - Nielsen, Anne-Louise

AU - Duelund, Lars

AU - Christensen, Morten

AU - Hervella, Pablo

AU - Needham, David

AU - Mouritsen, Ole G.

PY - 2016

Y1 - 2016

N2 - We have quantified the inhibition of intestinal cholesterol transport by pine-derived phytosterols using an HT29-MTX intestine cell model that forms a mucus layer similar to that in the intestine. An artificial intestinal fluid consisting of digested fat, bile salt, cholesterol, and phytosterols was formulated in order to mimic the conditions in the intestine. The apparent permeability coefficient (Papp) of the positive control, i.e., 0.1 mM of cholesterol solubilized in the artificial intestine fluid, was found to be 0.33 (± 0.17) × 10−6 cm/s. When 0.1 mM β-sitosterol was solubilized alongside, Papp was effectively zero, corresponding to a total inhibition of cholesterol transport. A similar strong inhibition was found when commercial pine-derived phytosterols, PinVita™ FSP DuPont, were co-solubilized with cholesterol in the dietary model micelles, leading to Papp = 0.06 (± 0.06) × 10−6 cm/s, i.e., 5.5 times lower than the cholesterol positive control. Additionally, the effect of potential oral administration formulations generated by the pine-derived phytosterols was also characterized. The formulations were produced as a liquid formulation of the cholesterol-containing artificial intestine fluid. Six liquid formulations were tested of which four displayed a Papp in the range of 0–0.09 × 10−6 cm/s. The remaining two formulations did not show any inhibition effect on cholesterol transport and even enhanced cholesterol transport. It was furthermore observed that the phytosterols were found in the collected intestine cells but not transported to the basolateral region in the intestinal cell model system.

AB - We have quantified the inhibition of intestinal cholesterol transport by pine-derived phytosterols using an HT29-MTX intestine cell model that forms a mucus layer similar to that in the intestine. An artificial intestinal fluid consisting of digested fat, bile salt, cholesterol, and phytosterols was formulated in order to mimic the conditions in the intestine. The apparent permeability coefficient (Papp) of the positive control, i.e., 0.1 mM of cholesterol solubilized in the artificial intestine fluid, was found to be 0.33 (± 0.17) × 10−6 cm/s. When 0.1 mM β-sitosterol was solubilized alongside, Papp was effectively zero, corresponding to a total inhibition of cholesterol transport. A similar strong inhibition was found when commercial pine-derived phytosterols, PinVita™ FSP DuPont, were co-solubilized with cholesterol in the dietary model micelles, leading to Papp = 0.06 (± 0.06) × 10−6 cm/s, i.e., 5.5 times lower than the cholesterol positive control. Additionally, the effect of potential oral administration formulations generated by the pine-derived phytosterols was also characterized. The formulations were produced as a liquid formulation of the cholesterol-containing artificial intestine fluid. Six liquid formulations were tested of which four displayed a Papp in the range of 0–0.09 × 10−6 cm/s. The remaining two formulations did not show any inhibition effect on cholesterol transport and even enhanced cholesterol transport. It was furthermore observed that the phytosterols were found in the collected intestine cells but not transported to the basolateral region in the intestinal cell model system.

KW - Apparent permeability coefficient

KW - Cholesterol

KW - HT29-MTX intestinal cell model

KW - Pine-derived phytosterols

KW - PinVita™ FSP DuPont

KW - Sterol transport

KW - β-Sitosterol

U2 - 10.1016/j.chemphyslip.2016.06.008

DO - 10.1016/j.chemphyslip.2016.06.008

M3 - Journal article

C2 - 27372052

AN - SCOPUS:84978839885

VL - 200

SP - 62

EP - 73

JO - Chemistry and Physics of Lipids

JF - Chemistry and Physics of Lipids

SN - 0009-3084

ER -