Dietary sphingomyelin suppresses intestinal cholesterol absorption by decreasing thermodynamic activity of cholesterol monomers

Erik R.M. Eckhardt, David Q.H. Wang, Joanne M. Donovan, Martin C. Carey

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Background & Aims: In humans, cholesterol absorbed from the intestine contributes appreciably to serum cholesterol levels. We hypothesized that cholesterol thermodynamic activity (At) would predict bioavailability of cholesterol monomers in intestinal content, and that natural dietary phospholipids exhibiting high affinity for cholesterol would reduce its absorption. Methods: Cholesterol At was determined by measuring partitioning of monomeric cholesterol from aqueous solutions of taurocholate, cholesterol, and either milk sphingomyelin (MSM), dipalmitoyl phosphatidylcholine (DPPC), or egg yolk phosphatidylcholine (EYPC) into wafers of polymerized silicone. Cholesterol absorption from the same mixtures was tested with monolayers of Caco-2 cells. For in vivo absorption studies (employing male C57L/J mice), we used the fecal dual isotope method during dietary enrichment with MSM, DPPC, or EYPC at varying dose levels. Results: Cholesterol At values were reduced significantly in MSM- and DPPC-containing systems compared with EYPC and correlated positively with reduced uptake and esterification of cholesterol by Caco-2 cells. Mice fed chow absorbed 31.4% ± 6.9% (mean ± SEM) cholesterol, whereas enrichment with MSM or DPPC led to dose-dependent decreases in cholesterol absorption; even at 0.1% MSM, cholesterol absorption was reduced by 20.4% ± 15.4% (P < 0.05, n = 6). Conclusions: Different phospholipids have distinct effects on micellar cholesterol At, which predicts cholesterol uptake by enterocytes in vitro as well as in vivo. Natural phospholipids with high affinity for cholesterol, as evidenced particularly by sphingomyelin, decrease At and curtail intestinal cholesterol absorption.

Original languageEnglish (US)
Pages (from-to)948-956
Number of pages9
JournalGastroenterology
Volume122
Issue number4
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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Sphingomyelins
Intestinal Absorption
Thermodynamics
Cholesterol
1,2-Dipalmitoylphosphatidylcholine
Milk
Egg Yolk
Phosphatidylcholines
Phospholipids
Caco-2 Cells
Taurocholic Acid
Gastrointestinal Contents
Enterocytes
Esterification
Silicones

ASJC Scopus subject areas

  • Gastroenterology

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Dietary sphingomyelin suppresses intestinal cholesterol absorption by decreasing thermodynamic activity of cholesterol monomers. / Eckhardt, Erik R.M.; Wang, David Q.H.; Donovan, Joanne M.; Carey, Martin C.

In: Gastroenterology, Vol. 122, No. 4, 01.01.2002, p. 948-956.

Research output: Contribution to journalArticle

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abstract = "Background & Aims: In humans, cholesterol absorbed from the intestine contributes appreciably to serum cholesterol levels. We hypothesized that cholesterol thermodynamic activity (At) would predict bioavailability of cholesterol monomers in intestinal content, and that natural dietary phospholipids exhibiting high affinity for cholesterol would reduce its absorption. Methods: Cholesterol At was determined by measuring partitioning of monomeric cholesterol from aqueous solutions of taurocholate, cholesterol, and either milk sphingomyelin (MSM), dipalmitoyl phosphatidylcholine (DPPC), or egg yolk phosphatidylcholine (EYPC) into wafers of polymerized silicone. Cholesterol absorption from the same mixtures was tested with monolayers of Caco-2 cells. For in vivo absorption studies (employing male C57L/J mice), we used the fecal dual isotope method during dietary enrichment with MSM, DPPC, or EYPC at varying dose levels. Results: Cholesterol At values were reduced significantly in MSM- and DPPC-containing systems compared with EYPC and correlated positively with reduced uptake and esterification of cholesterol by Caco-2 cells. Mice fed chow absorbed 31.4{\%} ± 6.9{\%} (mean ± SEM) cholesterol, whereas enrichment with MSM or DPPC led to dose-dependent decreases in cholesterol absorption; even at 0.1{\%} MSM, cholesterol absorption was reduced by 20.4{\%} ± 15.4{\%} (P < 0.05, n = 6). Conclusions: Different phospholipids have distinct effects on micellar cholesterol At, which predicts cholesterol uptake by enterocytes in vitro as well as in vivo. Natural phospholipids with high affinity for cholesterol, as evidenced particularly by sphingomyelin, decrease At and curtail intestinal cholesterol absorption.",
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N2 - Background & Aims: In humans, cholesterol absorbed from the intestine contributes appreciably to serum cholesterol levels. We hypothesized that cholesterol thermodynamic activity (At) would predict bioavailability of cholesterol monomers in intestinal content, and that natural dietary phospholipids exhibiting high affinity for cholesterol would reduce its absorption. Methods: Cholesterol At was determined by measuring partitioning of monomeric cholesterol from aqueous solutions of taurocholate, cholesterol, and either milk sphingomyelin (MSM), dipalmitoyl phosphatidylcholine (DPPC), or egg yolk phosphatidylcholine (EYPC) into wafers of polymerized silicone. Cholesterol absorption from the same mixtures was tested with monolayers of Caco-2 cells. For in vivo absorption studies (employing male C57L/J mice), we used the fecal dual isotope method during dietary enrichment with MSM, DPPC, or EYPC at varying dose levels. Results: Cholesterol At values were reduced significantly in MSM- and DPPC-containing systems compared with EYPC and correlated positively with reduced uptake and esterification of cholesterol by Caco-2 cells. Mice fed chow absorbed 31.4% ± 6.9% (mean ± SEM) cholesterol, whereas enrichment with MSM or DPPC led to dose-dependent decreases in cholesterol absorption; even at 0.1% MSM, cholesterol absorption was reduced by 20.4% ± 15.4% (P < 0.05, n = 6). Conclusions: Different phospholipids have distinct effects on micellar cholesterol At, which predicts cholesterol uptake by enterocytes in vitro as well as in vivo. Natural phospholipids with high affinity for cholesterol, as evidenced particularly by sphingomyelin, decrease At and curtail intestinal cholesterol absorption.

AB - Background & Aims: In humans, cholesterol absorbed from the intestine contributes appreciably to serum cholesterol levels. We hypothesized that cholesterol thermodynamic activity (At) would predict bioavailability of cholesterol monomers in intestinal content, and that natural dietary phospholipids exhibiting high affinity for cholesterol would reduce its absorption. Methods: Cholesterol At was determined by measuring partitioning of monomeric cholesterol from aqueous solutions of taurocholate, cholesterol, and either milk sphingomyelin (MSM), dipalmitoyl phosphatidylcholine (DPPC), or egg yolk phosphatidylcholine (EYPC) into wafers of polymerized silicone. Cholesterol absorption from the same mixtures was tested with monolayers of Caco-2 cells. For in vivo absorption studies (employing male C57L/J mice), we used the fecal dual isotope method during dietary enrichment with MSM, DPPC, or EYPC at varying dose levels. Results: Cholesterol At values were reduced significantly in MSM- and DPPC-containing systems compared with EYPC and correlated positively with reduced uptake and esterification of cholesterol by Caco-2 cells. Mice fed chow absorbed 31.4% ± 6.9% (mean ± SEM) cholesterol, whereas enrichment with MSM or DPPC led to dose-dependent decreases in cholesterol absorption; even at 0.1% MSM, cholesterol absorption was reduced by 20.4% ± 15.4% (P < 0.05, n = 6). Conclusions: Different phospholipids have distinct effects on micellar cholesterol At, which predicts cholesterol uptake by enterocytes in vitro as well as in vivo. Natural phospholipids with high affinity for cholesterol, as evidenced particularly by sphingomyelin, decrease At and curtail intestinal cholesterol absorption.

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