Absorbability of β-sitosterol in humans

Gould, R. Gordon; Jones, Richard J.; Leroy, Georges; Wissler, Robert W.; Taylor, Craig

doi:10.1016/0026-0495(69)90078-x

Cited by 149 publications

(67 citation statements)

References 7 publications

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“…Cows, for example, eat only foods that contain plant sterols, and yet their bodies contain cholesterol but not plant sterols. Investigations of such observations led to the discovery that plant sterols were excluded by the body, but could compete with bulk cholesterol for entry into the micelles formed during digestion, thus preventing dietary absorption of cholesterol [6,14,21,34,50,55,59]. Into this milieu of understanding, two key landmark observations led to a revolution in our current knowledge of how whole-body sterol balance may be achieved.…”

Section: Historicalmentioning

confidence: 99%

“…Into this milieu of understanding, two key landmark observations led to a revolution in our current knowledge of how whole-body sterol balance may be achieved. The context of the first landmark event was a knowledge that plant sterols were poorly absorbed relative to cholesterol [14], and that very high plasma cholesterol levels in humans were caused by a dominant genetic defect in the low-density lipoprotein receptor (and was associated with patients who developed accumulations of sterols in their tendons, called xanthomas). In a classic paper that should epitomize clinical investigation, Bhattacharyya and Connor described a new disease, named β-sitosterolemia, after identification of two sisters who had tendon xanthomas but did not have elevated plasma cholesterol, and who had very high amounts of plasma plant sterols, the major species of which was sitosterol, hence the name [3].…”

Section: Historicalmentioning

confidence: 99%

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Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols

Hazard

Patel

2006

Pflugers Arch - Eur J Physiol

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ABCG5 and ABCG8 are two ATP-binding cassette half-transporters that belong to the G family members. They were identified as proteins that are mutated in a rare human disorder, sitosterolemia, and their identification led to the completion of the physiological pathways by which dietary cholesterol, as well as noncholesterol sterols, traffics in the mammalian body. These proteins are likely to function as heterodimers, and current evidence suggests that these proteins are responsible for the majority of sterol secretions into bile, thus may define the long sought-after biliary sterol transporters. This review will focus on some of the backgrounds of this physiology, the genetics and regulation of these genes, as well as our current understanding of their functions. This review will also highlight the current limitations in our knowledge gap.

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Section: Historicalmentioning

confidence: 99%

Section: Historicalmentioning

confidence: 99%

Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols

Hazard

Patel

2006

Pflugers Arch - Eur J Physiol

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“…Sitosterolemic patients also accumulate other sterols in plasma including a variety of plant sterols (campesterol, stigmasterol, and avenasterol) and shellfish sterols (brassicasterol, 24-methylene cholesterol, and 22-dehydrocholesterol) (1,7). In normal individuals these sterols are poorly absorbed and preferentially secreted into the bile (8)(9)(10). These sterols comprise only Ϸ1% of plasma and tissue sterols in normal individuals but Ϸ15% of circulating and tissue sterols in sitosterolemia (11).…”

mentioning

confidence: 99%

Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion

Hammer

Li-Hawkins

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

647

605

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Cholesterol and other sterols exit the body primarily by secretion into bile. In patients with sitosterolemia, mutations in either of two ATP-binding cassette (ABC) half-transporters, ABCG5 or ABCG8, lead to reduced secretion of sterols into bile, implicating these transporters in this process. To elucidate the roles of ABCG5 and ABCG8 in the trafficking of sterols, we disrupted Abcg5 and Abcg8 in mice (G5G8 ؊/؊ ). The G5G8 ؊/؊ mice had a 2-to 3-fold increase in the fractional absorption of dietary plant sterols, which was associated with an Ϸ30-fold increase in plasma sitosterol. Biliary cholesterol concentrations were extremely low in the G5G8 ؊/؊ mice when compared with wild-type animals (mean ‫؍‬ 0.4 vs. 5.5 mol͞ml) and increased only modestly with cholesterol feeding. Plasma and liver cholesterol levels were reduced by 50% in the chow-fed G5G8 ؊/؊ mice and increased 2.4-and 18-fold, respectively, after cholesterol feeding. These data indicate that ABCG5 and ABCG8 are required for efficient secretion of cholesterol into bile and that disruption of these genes increases dramatically the responsiveness of plasma and hepatic cholesterol levels to changes in dietary cholesterol content.ATP-binding cassette transporters ͉ sitosterolemia ͉ bile ͉ knockout mice S itosterolemia is a rare autosomal recessive disorder characterized by the accumulation of plant and animal sterols in blood and tissues (1, 2). Affected subjects with this disorder develop large deposits of cholesterol in their skin, tendons, and coronary arteries. The accumulation of plant and animal sterols in the blood is caused by an increase in the fractional absorption of sterols from the diet and a decrease in the secretion of sterols into the bile, which is the major route of exit of sterols from the body (3, 4).A striking feature of sitosterolemia is the precipitous fall in plasma cholesterol that follows reductions in dietary cholesterol intake, especially in young patients (5, 6). When normal individuals are switched from a high cholesterol, high fat diet to a low cholesterol, low fat diet, plasma levels of cholesterol fall Ϸ10-20%; in patients with sitosterolemia, plasma cholesterol can fall by Ͼ45% (5, 6). The hypercholesterolemia of sitosterolemia is also sensitive to treatment with bile-acid resins, which stimulate the conversion of cholesterol to bile acids, another pathway for removal of cholesterol from the body.The pathognomonic feature of sitosterolemia is the elevation in plasma sitosterol, the most abundant plant sterol (1). Sitosterolemic patients also accumulate other sterols in plasma including a variety of plant sterols (campesterol, stigmasterol, and avenasterol) and shellfish sterols (brassicasterol, 24-methylene cholesterol, and 22-dehydrocholesterol) (1, 7). In normal individuals these sterols are poorly absorbed and preferentially secreted into the bile (8-10). These sterols comprise only Ϸ1% of plasma and tissue sterols in normal individuals but Ϸ15% of circulating and tissue sterols in sitosterolemia (11).Studies of sitoste...

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“…The most plentiful of these are the two plant sterols, sitosterol and campesterol. The levels of these sterols in tissues are very low, because plant sterols are poorly absorbed from the intestine and are preferentially secreted into the bile by hepatocytes (1)(2)(3).…”

mentioning

confidence: 99%

Stimulation of Cholesterol Excretion by the Liver X Receptor Agonist Requires ATP-binding Cassette Transporters G5 and G8

York

Bergmann

et al. 2003

Journal of Biological Chemistry

257

193

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Liver X receptor (LXR) is a nuclear receptor that plays a crucial role in orchestrating the trafficking of sterols between tissues. Treatment of mice with a potent and specific LXR agonist, T0901317, is associated with increased biliary cholesterol secretion, decreased fractional cholesterol absorption, and increased fecal neutral sterol excretion. Here we show that expression of two target genes of LXR␣, the ATP-binding cassette (ABC) transporters Abcg5 and Abcg8, is required for both the increase in sterol excretion and the decrease in fractional cholesterol absorption associated with LXR agonist treatment. Mice expressing no ABCG5 and ABCG8 (G5G8 ؊/؊ mice) and their littermate controls were treated for 7 days with T0901317. In wild type animals, treatment with the LXR agonist resulted in a 3-fold increase in biliary cholesterol concentrations, a 25% reduction in fractional cholesterol absorption, and a 4-fold elevation in fecal neutral sterol excretion. In contrast, the LXR agonist did not significantly affect biliary cholesterol levels, fractional cholesterol absorption, or neutral fecal sterol excretion in the G5G8 ؊/؊ mice. Thus Abcg5 and Abcg8 are required for LXR agonist-associated changes in dietary and biliary sterol trafficking. These results establish a central role for ABCG5 and ABCG8 in promoting cholesterol excretion in vivo.Cholesterol is an important structural component of animal cell membranes. The cholesterol required to maintain membrane integrity can be synthesized de novo from acetyl-CoA or can be obtained from cholesterol-containing foods in the diet. The typical Western diet includes ϳ400 mg of cholesterol per day, of which 40 -50% is absorbed in the proximal small intestine. The major pathway by which cholesterol is eliminated from the body is by excretion into bile either as free cholesterol or after conversion to bile acids.A variety of noncholesterol sterols are also present in the diet. The most plentiful of these are the two plant sterols, sitosterol and campesterol. The levels of these sterols in tissues are very low, because plant sterols are poorly absorbed from the intestine and are preferentially secreted into the bile by hepatocytes (1-3).One mechanism by which excess cholesterol and other sterols are eliminated from the body involves the action of two ATP-binding cassette (ABC) 1 half-transporters, ABCG5 and ABCG8 (4, 5). Mutations in either of these genes cause sitosterolemia, a rare autosomal recessive disorder of sterol trafficking (4, 5). Subjects with sitosterolemia have increased fractional absorption of dietary noncholesterol sterols and decreased biliary secretion of plant-and animal-derived sterols (6, 7). Consequently, these patients accumulate sitosterol, as well as other plant-and shellfish-derived neutral sterols, in the blood and tissues (8, 9). Subjects with sitosterolemia also are frequently hypercholesterolemic and develop tendon xanthomas and premature coronary artery disease (8, 10).The pivotal role of ABCG5 and ABCG8 in enterohepatic sterol transport has ...

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Absorbability of β-sitosterol in humans

Cited by 149 publications

References 7 publications

Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols

Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols

Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion

Stimulation of Cholesterol Excretion by the Liver X Receptor Agonist Requires ATP-binding Cassette Transporters G5 and G8

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