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World J Gastroenterol. Dec 21, 2010; 16(47): 5953-5957
Published online Dec 21, 2010. doi: 10.3748/wjg.v16.i47.5953
From blood to gut: Direct secretion of cholesterol via transintestinal cholesterol efflux
Carlos LJ Vrins
Carlos LJ Vrins, Department of Medical Biochemistry, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands
Author contributions: Vrins CLJ solely contributed to this paper.
Correspondence to: Dr. Carlos LJ Vrins, PhD, Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.
Telephone: +31-20-5665136 Fax: +31-20-6915519
Received: July 2, 2010
Revised: July 28, 2010
Accepted: August 5, 2010
Published online: December 21, 2010


The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol-lowering therapies. By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body. For a long time this removal via the hepatobiliary secretion was considered to be the sole route involved in the RCT. However, observations from early studies in animals and humans already pointed towards the possibility of another route. In the last few years it has become evident that a non-biliary cholesterol secretion pathway exists in which the intestine plays a central role. This transintestinal cholesterol efflux (TICE) pathway contributes significantly to the total fecal neutral sterol excretion. Moreover, recent studies have shown that TICE is also sensitive to stimulation. As a consequence, the direct role of cholesterol secretion from blood via TICE makes the intestine a suitable and approachable target for cholesterol removal from the body and possibly reduction of atherosclerosis. In this review, the discovery and recent findings contributing to understanding the mechanism of TICE will be discussed.

Key Words: Cholesterol, Intestine, Transintestinal cholesterol efflux


Since the introduction of statins about 25 years ago, therapeutic lowering of cholesterol levels has been proven successful in decreasing the incidence of cardiovascular diseases (CVDs)[1]. In fact, the reduction of low density lipoprotein (LDL) cholesterol levels in blood by the inhibition of cholesterol biosynthesis using these 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors is still the most potent cholesterol-lowering therapy to date[2]. However, while the reduction of LDL cholesterol levels in blood helps to prevent the development of atherosclerosis, the underlying process of CVD, it does not seem to be sufficient enough for the reversal of already existing atherosclerotic lesions[3,4]. With better understanding of cholesterol metabolism, new ideas for therapies to prevent CVD have emerged. One of the most prominent attempts in the last decade is stimulating reverse cholesterol transport (RCT)[5-7]. RCT describes the different stages of cholesterol transport, from efflux from peripheral tissues to fecal excretion[8]. Passage through liver and bile before subsequent entry into the intestinal lumen has long been considered to be the most important, if not the only, route in RCT. However recent findings have shown the existence of a cholesterol secretion pathway that is independent of this hepatobiliary tract[9,10].


Since the introduction of the term RCT in the early 1970s, our knowledge of this cholesterol removal pathway has advanced to a great extent[8]. In brief, the pathway starts with the efflux of cholesterol from peripheral cells, including from macrophages in the arterial wall, by cholesterol transporters adenosine triphosphate-binding cassette transporter protein (ABC) A1 and G1 (Figure 1)[6,7]. This cholesterol is transported via lipoproteins to the liver where it can be taken up by hepatocytes via specific lipoprotein receptors. The lipoprotein that mediates this transport is the high density lipoprotein (HDL). However, recent findings in transgenic mice also include a role for LDL via the activity of cholesteryl ester transfer protein[11]. After uptake at the basolateral side, the cholesterol can be transferred to the bile via secretion at the canalicular membrane of the hepatocyte. The cholesterol transport over the canalicular membrane is mainly facilitated by a heterodimer complex formed by ABCG5 and ABCG8[12]. Biliary cholesterol enters the intestinal lumen, from where a significant amount is re-absorbed by the enterocytes[13]. The remaining cholesterol leaves the body via fecal excretion.

Figure 1
Figure 1 Schematic overview of the reverse cholesterol transport pathways. ABCA1: Adenosine triphosphate (ATP)-binding cassette transporter A1; ABCG1: ATP-binding cassette transporter G1; ABCG5: ATP-binding cassette transporter G5; ABCG8: ATP-binding cassette transporter G8; SR-BI: Scavenger receptor class B type I; TICE: Transintestinal cholesterol efflux.

This hepatobiliary pathway was considered to be the sole route for cholesterol secretion from the body. In vivo cholesterol balance studies in wild type and mouse models with abrogated biliary cholesterol secretion have, however, suggested the existence of an alternative direct cholesterol transport route from blood to the intestine.


If the fecal sterol output only depends on the hepatobiliary cholesterol transport, it should directly be affected by diminished biliary cholesterol secretion. Hence, fecal sterol excretion should be attenuated in mice lacking a functional ABCG5/ABCG8 or deficient for phospholipid transporter ABCG4. Interestingly, despite the very low to absent biliary cholesterol secretion in these mice their sterol output is similar to that of their wild type littermates[9,12,14]. The idea that the fecal sterol excretion might to a certain extent be independent of biliary cholesterol secretion is not confined to recent observations. Earlier findings going as far back as the beginning of the last century already suggested the existence of an additional source for cholesterol excretion. In 1927, Sperry[15] reported that he had measured more excreted cholesterol in the feces of dogs with bile fistula than he would have predicted based on the results obtained from control dogs; an observation which was confirmed 50 years later by Pertsemlidis et al[16]. It was also observed in rats that a large part of the cholesterol that ends up in the feces seems to originate from a source other than bile and diet[17,18].

To test the possibility that the intestine is not only responsible for the uptake of cholesterol but also is actively involved in the secretion of cholesterol, intestine perfusions were performed in mice[9]. In these experiments the bile duct was ligated and the bile itself was diverted via gallbladder cannulation. Subsequently, a section of the small intestine was perfused with a buffered solution containing a mixture of bile salts and phospholipids. This procedure allows a determination of the contribution of biliary cholesterol secretion, as well as that of transintestinal cholesterol secretion, to the total fecal neutral sterol output. This method demonstrated that a considerable amount of cholesterol is secreted by the small intestine. The secretion takes place over the entire length of the small intestine but it is most significant in the proximal part. The majority of this secreted cholesterol does not find its origin in the high turnover of enterocytes and does not correlate with cholesterol synthesis in the enterocytes. Moreover, intestine perfusions performed on mice that were intravenously injected with radiolabeled cholesterol established the direct secretion of cholesterol from blood through the intestinal wall into the intestinal lumen[9,19]. Surprisingly, these reports also showed that this transintestinal cholesterol efflux (TICE) pathway in mice plays a more prominent role in the excretion of cholesterol than the hepatobiliary route.

While the intestine perfusions in mice showed for the first time the existence of TICE, a recent study by Brown et al[10] also unmistakingly showed the presence of a non-biliary route for cholesterol excretion. In their report, mice deficient for hepatic acyl-CoA: cholesterol O-acyltransferase 2 (ACAT2) had an increased fecal excretion of cholesterol without a changed biliary cholesterol secretion. Additionally, they also found intestinal cholesterol secretion to be the highest in the proximal small intestine.

With the evidence that the small intestine is not only involved in the uptake of cholesterol but also has the ability to actively secrete cholesterol, a new potentially attractive target for therapeutic lowering of cholesterol has emerged. However, more understanding of the mechanism of TICE is required.


Several studies in mice have demonstrated that the activity of TICE can be stimulated. One of our earliest studies on TICE involved the sensitivity of this novel pathway to dietary manipulations. When mice are fed a high lipid diet, fecal neutral sterol excretion is increased[20-22]. Besides the higher input of cholesterol, this increase upon feeding with diets containing high cholesterol can be explained by reduced intestinal uptake of cholesterol and increased biliary cholesterol secretion. However, the increased fecal neutral sterol excretion seen in mice fed a high fat diet without cholesterol did not correlate with increased biliary cholesterol secretion. We studied the effect of high lipid diets on TICE and found that the secretion of cholesterol by the intestine is also increased in mice fed a western-type diet, containing high cholesterol and high fat[9]. Interestingly, a high cholesterol-only diet did not affect TICE suggesting that this secretion pathway is responsive to the fat content of the western-type diet[21]. This was confirmed in mice that were fed a high-fat diet without cholesterol. We also showed that activation of the peroxisome proliferator-activated receptor δ (PPARδ) caused an over two-fold increase in TICE[23]. This finding strengthened the link between TICE and fat metabolism since polyunsaturated fatty acids are natural ligands of this member of the nuclear receptor family[24].

Another nuclear receptor that is involved in the regulation of lipid-related metabolic processes, the liver X receptor (LXR), affects TICE as well[19,25]. In mice, activation of LXR increased fecal neutral sterol loss independent of biliary cholesterol secretion. However, the stimulation of TICE upon a high fat diet in LXRα knock-out mice suggests that LXR sensitivity of TICE occurs via a different pathway[22].

The effect of luminal modifications on TICE was investigated by means of introducing different combinations of bile salt-phospholipid[21]. Although the intraluminal presence of bile salts was crucial for TICE, an important finding was that, in contrast to biliary cholesterol secretion, TICE seemed to be insensitive to both the type of bile salt and bile salt concentration. The presence of intraluminal phospholipids was not essential for TICE. However, the addition of phospholipids did have a stimulatory effect on TICE.


To gain better insight into this RCT pathway and identify key players in the intestine, the ability to stimulate the rate of TICE may be a helpful tool (Figure 2). Unfortunately, expression analysis of cholesterol-related genes in the small intestine from mice fed with a high-fat diet or treated with PPARδ agonist did not reveal many usual suspects[21,22]. The gene expression of the key factor in cholesterol synthesis, i.e. 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr), was unaffected and the expression of most genes encoding cholesterol transporters was either unchanged or even decreased. One transporter that was upregulated in the small intestine of mice that received a high-fat diet was the scavenger receptor class B type I (SR-BI). Although it can mediate uptake from both LDL and HDL, SR-BI is mostly involved in the cellular cholesterol uptake from circulating HDL[26,27]. Considering their well accepted role in RCT via the hepatobiliary route, a comparable role for both SR-BI and HDL in TICE is plausible. However, a direct involvement of SR-BI has become debatable since TICE was also increased in mice deficient for SR-BI[21]. Also, Sr-b1-/- mice are characterized by elevated HDL-levels[28], but a possible relationship between the physiologic concentration of HDL and the rate of TICE is questionable. In Abca1-/- mice, which are characterized by low HDL levels and unaltered biliary cholesterol secretion, no decrease in fecal neutral sterol excretion has been observed[29]. In addition, Briand et al[30] demonstrated in wild type mice that uptake of HDL by the intestine is significantly lower than the hepatic uptake. Taken together, these data dispute the direct involvement of the major players in the hepatobiliary route. How, and by which cholesterol donor, the cholesterol is transported to the intestine for TICE remains to be elucidated. However, the link that has been established between TICE and deficiency in hepatic cholesterol esterification due to liver-specific depletion of ACAT2 might help to shed some light on this part of the non-hepatobiliary cholesterol secretion route[10].

Figure 2
Figure 2 Enterocyte representation with a schematic overview of cholesterol transporters and potential transintestinal cholesterol efflux-related factors as discussed in this paper. PPARδ: Peroxisome proliferator-activated receptor δ; LXR: Liver X receptor; LDLR: Low density lipoprotein receptor; SR-BI: Scavenger receptor class B type I; ABCA1: Adenosine triphosphate (ATP)-binding cassette transporter A1; ABCG5: ATP-binding cassette transporter G5; ABCG8: ATP-binding cassette transporter G8; Hmgcr: 3-hydroxy-3-methyl-glutaryl-CoA reductase; Limp2: Lysosomal integral membrane protein 2; NPC1L1: Niemann-Pick C1-like 1 protein; TICE: Transintestinal cholesterol efflux.

One important cholesterol transporter that was affected in both high-fat diet-fed and PPARδ agonist-treated mice, was the Niemann-Pick C1-like 1 protein (NPC1L1)[21,23]. Earlier reports could only partially explain the increased fecal neutral sterol output by the reduced cholesterol absorption caused by the attenuated expression of NPC1L1[22,31]. Despite the strong increase in fecal neutral sterol excretion in mice upon treatment with ezetimibe, the inhibitor of NPC1L1, we have shown that NPC1L1 plays no role in TICE[23].

Interestingly, gene expression analysis in the intestine of mice with an increased TICE did reveal two genes encoding proteins that have been associated with the intracellular transport of cholesterol[23]. Rab9 plays a role in cholesterol trafficking from late endosomes to the trans-Golgi network and it has been shown that overexpression of Rab9 can relieve cholesterol build up in Niemann-Pick type C cells, which is a manifestation of a lipid storage disorder[32,33].

The lysosomal integral membrane protein 2 (Limp2) is a lysosomal membrane protein that is known to bind to β-glucocerebrosidase and has specific functions in intracellular vesicular trafficking[34]. However, Limp2 is also the mouse ortholog of the human scavenger receptor class B type 2 (Scarb2) which has been shown to influence cholesterol homeostasis[35]. What the exact relationship between these two factors and TICE might be requires further studies.

Finally, a role for the heterodimer ABCG5/G8 in TICE cannot be ruled out. Despite being a likely candidate for mediating cholesterol secretion into the intestinal lumen in TICE, initial studies in mice lacking functional ABCG5/G8, as mentioned above, only helped in pointing out the existence of TICE. Since TICE was not reduced in Abcg8-/- mice, a possible function for ABCG5/G8 in TICE was questionable[9]. However, a more recent study from van der Veen et al[19] demonstrated that increase in TICE upon LXR agonist treatment was ABCG5/G8-dependent.


Many cholesterol lowering therapies under development are aimed at increasing cholesterol excretion by stimulation of RCT. Recent studies in mice have now confirmed the presence of direct cholesterol secretion via the intestine. The contribution of TICE in mice to cholesterol excretion is even more prominent than that of the biliary cholesterol secretion. Of course, these observations do not constitute the existence and relevance of TICE in humans. However, by the late sixties Simmonds et al[36] had already observed cholesterol secretion in the small intestine after performing intestine perfusions in humans. Our group recently estimated that in humans TICE might amount to around one-third of biliary cholesterol secretion, based on average dietary cholesterol intake, biliary cholesterol secretion, and cholesterol excretion in humans[9]. Nonetheless, the exact contribution of TICE in humans still needs to be quantified. Interestingly, it has been documented that the identified and aforementioned stimulators of TICE in mice also have a positive effect on cholesterol excretion in humans. In mice, the secretion of cholesterol by the intestine could be induced by high fat diets and regulated by the phospholipid content in the intestinal lumen[21]. Several studies in men have shown that diets enriched with polyunsaturated fatty acids increase fecal sterol excretion[37-39]. Furthermore, the supplementation of phospholipids strongly stimulated the excretion of sterols in the feces in humans[40].

We are still challenged by a better understanding of the mechanistic details of this novel RCT pathway, but it is clear that TICE presents us with a therapeutic potential in the treatment of atherosclerosis. The direct role of the intestine in the reverse transport of cholesterol from “blood to gut” makes it a suitable and approachable target for cholesterol removal from the body and prevention of cardiovascular diseases.


Peer reviewer: Adriana M Torres, Professor of Pharmacology, Faculty of Biochemical and Pharmaceutical Sciences, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina

S- Editor Wang JL L- Editor Logan S E- Editor Lin YP

1.  Tobert JA. Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov. 2003;2:517-526.  [PubMed]  [DOI]  [Cited in This Article: ]
2.  Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267-1278.  [PubMed]  [DOI]  [Cited in This Article: ]
3.  Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet. 1994;344:1383-1389.  [PubMed]  [DOI]  [Cited in This Article: ]
4.  Venkatesh PK, Caskey D, Reddy PC. Therapies to increase high-density lipoprotein cholesterol and their effect on cardiovascular outcomes and regression of atherosclerosis. Am J Med Sci. 2008;336:64-68.  [PubMed]  [DOI]  [Cited in This Article: ]
5.  Chapman MJ. Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary heart disease. Pharmacol Ther. 2006;111:893-908.  [PubMed]  [DOI]  [Cited in This Article: ]
6.  Rader DJ. Mechanisms of disease: HDL metabolism as a target for novel therapies. Nat Clin Pract Cardiovasc Med. 2007;4:102-109.  [PubMed]  [DOI]  [Cited in This Article: ]
7.  Tall AR. Cholesterol efflux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins. J Intern Med. 2008;263:256-273.  [PubMed]  [DOI]  [Cited in This Article: ]
8.  Glomset JA, Norum KR. The metabolic role of lecithin: cholesterol acyltransferase: perspectives form pathology. Adv Lipid Res. 1973;11:1-65.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  van der Velde AE, Vrins CL, van den Oever K, Kunne C, Oude Elferink RP, Kuipers F, Groen AK. Direct intestinal cholesterol secretion contributes significantly to total fecal neutral sterol excretion in mice. Gastroenterology. 2007;133:967-975.  [PubMed]  [DOI]  [Cited in This Article: ]
10.  Brown JM, Bell TA 3rd, Alger HM, Sawyer JK, Smith TL, Kelley K, Shah R, Wilson MD, Davis MA, Lee RG. Targeted depletion of hepatic ACAT2-driven cholesterol esterification reveals a non-biliary route for fecal neutral sterol loss. J Biol Chem. 2008;283:10522-10534.  [PubMed]  [DOI]  [Cited in This Article: ]
11.  Tanigawa H, Billheimer JT, Tohyama J, Zhang Y, Rothblat G, Rader DJ. Expression of cholesteryl ester transfer protein in mice promotes macrophage reverse cholesterol transport. Circulation. 2007;116:1267-1273.  [PubMed]  [DOI]  [Cited in This Article: ]
12.  Yu L, Hammer RE, Li-Hawkins J, Von Bergmann K, Lutjohann D, Cohen JC, Hobbs HH. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci USA. 2002;99:16237-16242.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Wang DQ, Carey MC. Measurement of intestinal cholesterol absorption by plasma and fecal dual-isotope ratio, mass balance, and lymph fistula methods in the mouse: an analysis of direct versus indirect methodologies. J Lipid Res. 2003;44:1042-1059.  [PubMed]  [DOI]  [Cited in This Article: ]
14.  Smit JJ, Schinkel AH, Oude Elferink RP, Groen AK, Wagenaar E, van Deemter L, Mol CA, Ottenhoff R, van der Lugt NM, van Roon MA. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell. 1993;75:451-462.  [PubMed]  [DOI]  [Cited in This Article: ]
15.  Sperry WM. Lipid excretion IV. A study of the relationship of the bile to the fecal lipids with special reference to certain problems of sterol metabolism. J Biol Chem. 1927;71:351-378.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Pertsemlidis D, Kirchman EH, Ahrens EH Jr. Regulation of cholesterol metabolism in the dog. I. Effects of complete bile diversion and of cholesterol feeding on absorption, synthesis, accumulation, and excretion rates measured during life. J Clin Invest. 1973;52:2353-2367.  [PubMed]  [DOI]  [Cited in This Article: ]
17.  Miettinen TA, Proia A, McNamara DJ. Origins of fecal neutral steroids in rats. J Lipid Res. 1981;22:485-495.  [PubMed]  [DOI]  [Cited in This Article: ]
18.  Bandsma RH, Kuipers F, Vonk RJ, Boverhof R, Sauer PJ, Nagel GT, Elzinga H, Neese RA, Hellerstein MK, Stellaard F. The contribution of newly synthesized cholesterol to bile salt synthesis in rats quantified by mass isotopomer distribution analysis. Biochim Biophys Acta. 2000;1483:343-351.  [PubMed]  [DOI]  [Cited in This Article: ]
19.  van der Veen JN, van Dijk TH, Vrins CL, van Meer H, Havinga R, Bijsterveld K, Tietge UJ, Groen AK, Kuipers F. Activation of the liver X receptor stimulates trans-intestinal excretion of plasma cholesterol. J Biol Chem. 2009;284:19211-19219.  [PubMed]  [DOI]  [Cited in This Article: ]
20.  Sehayek E, Ono JG, Shefer S, Nguyen LB, Wang N, Batta AK, Salen G, Smith JD, Tall AR, Breslow JL. Biliary cholesterol excretion: a novel mechanism that regulates dietary cholesterol absorption. Proc Natl Acad Sci USA. 1998;95:10194-10199.  [PubMed]  [DOI]  [Cited in This Article: ]
21.  van der Velde AE, Vrins CL, van den Oever K, Seemann I, Oude Elferink RP, van Eck M, Kuipers F, Groen AK. Regulation of direct transintestinal cholesterol excretion in mice. Am J Physiol Gastrointest Liver Physiol. 2008;295:G203-G208.  [PubMed]  [DOI]  [Cited in This Article: ]
22.  de Vogel-van den Bosch HM, de Wit NJ, Hooiveld GJ, Vermeulen H, van der Veen JN, Houten SM, Kuipers F, Müller M, van der Meer R. A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1171-G1180.  [PubMed]  [DOI]  [Cited in This Article: ]
23.  Vrins CL, van der Velde AE, van den Oever K, Levels JH, Huet S, Oude Elferink RP, Kuipers F, Groen AK. Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux. J Lipid Res. 2009;50:2046-2054.  [PubMed]  [DOI]  [Cited in This Article: ]
24.  Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, Sternbach DD, Lehmann JM, Wisely GB, Willson TM. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 1999;3:397-403.  [PubMed]  [DOI]  [Cited in This Article: ]
25.  Kruit JK, Plösch T, Havinga R, Boverhof R, Groot PH, Groen AK, Kuipers F. Increased fecal neutral sterol loss upon liver X receptor activation is independent of biliary sterol secretion in mice. Gastroenterology. 2005;128:147-156.  [PubMed]  [DOI]  [Cited in This Article: ]
26.  Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science. 1996;271:518-520.  [PubMed]  [DOI]  [Cited in This Article: ]
27.  Stangl H, Hyatt M, Hobbs HH. Transport of lipids from high and low density lipoproteins via scavenger receptor-BI. J Biol Chem. 1999;274:32692-32698.  [PubMed]  [DOI]  [Cited in This Article: ]
28.  Rigotti A, Trigatti BL, Penman M, Rayburn H, Herz J, Krieger M. A targeted mutation in the murine gene encoding the high density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism. Proc Natl Acad Sci USA. 1997;94:12610-12615.  [PubMed]  [DOI]  [Cited in This Article: ]
29.  Groen AK, Bloks VW, Bandsma RH, Ottenhoff R, Chimini G, Kuipers F. Hepatobiliary cholesterol transport is not impaired in Abca1-null mice lacking HDL. J Clin Invest. 2001;108:843-850.  [PubMed]  [DOI]  [Cited in This Article: ]
30.  Briand F, Naik SU, Fuki I, Millar JS, Macphee C, Walker M, Billheimer J, Rothblat G, Rader DJ. Both the peroxisome proliferator-activated receptor delta agonist, GW0742, and ezetimibe promote reverse cholesterol transport in mice by reducing intestinal reabsorption of HDL-derived cholesterol. Clin Transl Sci. 2009;2:127-133.  [PubMed]  [DOI]  [Cited in This Article: ]
31.  van der Veen JN, Kruit JK, Havinga R, Baller JF, Chimini G, Lestavel S, Staels B, Groot PH, Groen AK, Kuipers F. Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1. J Lipid Res. 2005;46:526-534.  [PubMed]  [DOI]  [Cited in This Article: ]
32.  Choudhury A, Dominguez M, Puri V, Sharma DK, Narita K, Wheatley CL, Marks DL, Pagano RE. Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells. J Clin Invest. 2002;109:1541-1550.  [PubMed]  [DOI]  [Cited in This Article: ]
33.  Narita K, Choudhury A, Dobrenis K, Sharma DK, Holicky EL, Marks DL, Walkley SU, Pagano RE. Protein transduction of Rab9 in Niemann-Pick C cells reduces cholesterol storage. FASEB J. 2005;19:1558-1560.  [PubMed]  [DOI]  [Cited in This Article: ]
34.  Eskelinen EL, Tanaka Y, Saftig P. At the acidic edge: emerging functions for lysosomal membrane proteins. Trends Cell Biol. 2003;13:137-145.  [PubMed]  [DOI]  [Cited in This Article: ]
35.  Eckhardt ER, Cai L, Sun B, Webb NR, van der Westhuyzen DR. High density lipoprotein uptake by scavenger receptor SR-BII. J Biol Chem. 2004;279:14372-14381.  [PubMed]  [DOI]  [Cited in This Article: ]
36.  Simmonds WJ, Hofmann AF, Theodor E. Absorption of cholesterol from a micellar solution: intestinal perfusion studies in man. J Clin Invest. 1967;46:874-890.  [PubMed]  [DOI]  [Cited in This Article: ]
37.  Connor WE, Witiak DT, Stone DB, Armstrong ML. Cholesterol balance and fecal neutral steroid and bile acid excretion in normal men fed dietary fats of different fatty acid composition. J Clin Invest. 1969;48:1363-1375.  [PubMed]  [DOI]  [Cited in This Article: ]
38.  Nestel PJ, Havenstein N, Homma Y, Scott TW, Cook LJ. Increased sterol excretion with polyunsaturated-fat high-cholesterol diets. Metabolism. 1975;24:189-198.  [PubMed]  [DOI]  [Cited in This Article: ]
39.  Oh SY, Monaco PA. Effect of dietary cholesterol and degree of fat unsaturation on plasma lipid levels, lipoprotein composition, and fecal steroid excretion in normal young adult men. Am J Clin Nutr. 1985;42:399-413.  [PubMed]  [DOI]  [Cited in This Article: ]
40.  Greten H, Raetzer H, Stiehl A, Schettler G. The effect of polyunsaturated phosphatidylcholine on plasma lipids and fecal sterol excretion. Atherosclerosis. 1980;36:81-88.  [PubMed]  [DOI]  [Cited in This Article: ]