Role of intestinal sterol transporters Abcg5, Abcg8, and Npc111 in cholesterol absorption in mice

Gender and age effects

Li Ping Duan, Helen H. Wang, Akira Ohashi, David Q.H. Wang

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Recent studies have indicated that intestinal cholesterol absorption is a multistep process, which is regulated by multiple genes at the enterocyte level. However, the molecular mechanisms whereby there are gender differences in intestinal cholesterol absorption efficiency and the efficiency of cholesterol absorption increases with age have not yet been fully understood. To explore whether aging increases cholesterol absorption via intestinal sterol transporters, we studied the higher cholesterol-absorbing C57L/J vs. the lower cholesterol-absorbing AKR/J mice at 8 (young adult), 36 (older adult), and 50 (aged) wk of age. To test the hypothesis that estrogen receptor (ER)α plays an important regulatory role in cholesterol absorption, we investigated the gonadectomized mice of both genders treated with 17β-estradiol- releasing pellets at 0, 3, or 6 μg/day and antiestrogenic ICI 182,780 at 125 μg/day. We found that hepatic outputs of biliary cholesterol were significantly increased with age and in response to high levels of estrogen. Aging significantly enhances cholesterol absorption by suppressing expression of the jejunal and ileal sterol efflux transporters [ATP-binding cassette (Abc)g5 and Abcg8] and upregulating expression of the putative duodenal and jejunal sterol influx transporter Npc1l1. Estrogen significantly augmented cholesterol absorption mostly due to an upregulated expression of intestinal Npc1l1, Abcg5, and Abcg8 via the intestinal ERα pathway, which can be fully abolished by the antagonist. We conclude that ERα activated by estrogen and aging enhances cholesterol absorption by increasing biliary lipid output and mediating intestinal sterol transporters favoring influx of intraluminal cholesterol molecules across the apical membrane of the enterocyte.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume290
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

Fingerprint

Sterols
Cholesterol
Intestinal Absorption
Estrogen Receptors
Estrogens
Enterocytes
Inbred AKR Mouse
ATP-Binding Cassette Transporters
Young Adult
Estradiol
Lipids

Keywords

  • Bile
  • Bile salt
  • Biliary secretion
  • Chylomicron
  • Genetics
  • Intestinal lipid uptake
  • Lymph
  • Micelle
  • Nutrition
  • Phospholipid

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

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title = "Role of intestinal sterol transporters Abcg5, Abcg8, and Npc111 in cholesterol absorption in mice: Gender and age effects",
abstract = "Recent studies have indicated that intestinal cholesterol absorption is a multistep process, which is regulated by multiple genes at the enterocyte level. However, the molecular mechanisms whereby there are gender differences in intestinal cholesterol absorption efficiency and the efficiency of cholesterol absorption increases with age have not yet been fully understood. To explore whether aging increases cholesterol absorption via intestinal sterol transporters, we studied the higher cholesterol-absorbing C57L/J vs. the lower cholesterol-absorbing AKR/J mice at 8 (young adult), 36 (older adult), and 50 (aged) wk of age. To test the hypothesis that estrogen receptor (ER)α plays an important regulatory role in cholesterol absorption, we investigated the gonadectomized mice of both genders treated with 17β-estradiol- releasing pellets at 0, 3, or 6 μg/day and antiestrogenic ICI 182,780 at 125 μg/day. We found that hepatic outputs of biliary cholesterol were significantly increased with age and in response to high levels of estrogen. Aging significantly enhances cholesterol absorption by suppressing expression of the jejunal and ileal sterol efflux transporters [ATP-binding cassette (Abc)g5 and Abcg8] and upregulating expression of the putative duodenal and jejunal sterol influx transporter Npc1l1. Estrogen significantly augmented cholesterol absorption mostly due to an upregulated expression of intestinal Npc1l1, Abcg5, and Abcg8 via the intestinal ERα pathway, which can be fully abolished by the antagonist. We conclude that ERα activated by estrogen and aging enhances cholesterol absorption by increasing biliary lipid output and mediating intestinal sterol transporters favoring influx of intraluminal cholesterol molecules across the apical membrane of the enterocyte.",
keywords = "Bile, Bile salt, Biliary secretion, Chylomicron, Genetics, Intestinal lipid uptake, Lymph, Micelle, Nutrition, Phospholipid",
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T1 - Role of intestinal sterol transporters Abcg5, Abcg8, and Npc111 in cholesterol absorption in mice

T2 - Gender and age effects

AU - Duan, Li Ping

AU - Wang, Helen H.

AU - Ohashi, Akira

AU - Wang, David Q.H.

PY - 2006/2/1

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N2 - Recent studies have indicated that intestinal cholesterol absorption is a multistep process, which is regulated by multiple genes at the enterocyte level. However, the molecular mechanisms whereby there are gender differences in intestinal cholesterol absorption efficiency and the efficiency of cholesterol absorption increases with age have not yet been fully understood. To explore whether aging increases cholesterol absorption via intestinal sterol transporters, we studied the higher cholesterol-absorbing C57L/J vs. the lower cholesterol-absorbing AKR/J mice at 8 (young adult), 36 (older adult), and 50 (aged) wk of age. To test the hypothesis that estrogen receptor (ER)α plays an important regulatory role in cholesterol absorption, we investigated the gonadectomized mice of both genders treated with 17β-estradiol- releasing pellets at 0, 3, or 6 μg/day and antiestrogenic ICI 182,780 at 125 μg/day. We found that hepatic outputs of biliary cholesterol were significantly increased with age and in response to high levels of estrogen. Aging significantly enhances cholesterol absorption by suppressing expression of the jejunal and ileal sterol efflux transporters [ATP-binding cassette (Abc)g5 and Abcg8] and upregulating expression of the putative duodenal and jejunal sterol influx transporter Npc1l1. Estrogen significantly augmented cholesterol absorption mostly due to an upregulated expression of intestinal Npc1l1, Abcg5, and Abcg8 via the intestinal ERα pathway, which can be fully abolished by the antagonist. We conclude that ERα activated by estrogen and aging enhances cholesterol absorption by increasing biliary lipid output and mediating intestinal sterol transporters favoring influx of intraluminal cholesterol molecules across the apical membrane of the enterocyte.

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KW - Bile

KW - Bile salt

KW - Biliary secretion

KW - Chylomicron

KW - Genetics

KW - Intestinal lipid uptake

KW - Lymph

KW - Micelle

KW - Nutrition

KW - Phospholipid

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DO - 10.1152/ajpgi.00172.2005

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JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

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