Cholesterol absorption in rat intestine: role of cholesterol esterase and acyl coenzyme A:cholesterol acyltransferase.

Atherosclerosis has a strong dietary basis without a proven molecular mechanism for cholesterol absorption. To investigate the potential role of pancreas in this process and its interaction with the two dietary forms of cholesterol (free and esterified), we undertook to study the role of pancreatic cholesterol esterase in cholesterol absorption. The results showed that (i) cholesterol esters contribute a disproportionately high fraction of absorbed dietary cholesterol, (ii) rates of intestinal cholesterol absorption are related to pancreatic cholesterol esterase activity, (iii) mRNA specific for pancreatic cholesterol esterase is induced 15-fold by dietary sterol esters and 10-fold by free sterol, (iv) the induction of cholesterol esterase mRNA is reversible, and (v) free cholesterol transport into cultured human intestinal cells is enhanced 300% by pancreatic cholesterol esterase. These data implicate pancreatic cholesterol esterase as pivotal in a metabolic loop under positive feedback control for the absorption of dietary cholesterol, whether free or esterified.Key words: cholesterol esterase, diet, transport, mRNA, induction.

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Pancreatic trypsin cleaves intestinal alkaline sphingomyelinase from mucosa and enhances the sphingomyelinase activity

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00190.2004 ◽

2004 ◽

Vol 287 (5) ◽

pp. G967-G973 ◽

Cited By ~ 21

Author(s):

Jun Wu ◽

Fuli Liu ◽

Åke Nilsson ◽

Rui-Dong Duan

Keyword(s):

Culture Medium ◽

Physiological Role ◽

Cholesterol Absorption ◽

Full Length ◽

Rat Intestine ◽

His Tag ◽

Alkaline Sphingomyelinase ◽

Luminal Perfusion ◽

Signal Anchor

Sphingomyelin (SM) hydrolysis in the gut has implications in colonic tumorigenesis and cholesterol absorption. It is triggered by intestinal alkaline sphingomyelinase (Alk-SMase) that is present in the intestinal mucosa and content. The mechanism by which the enzyme is released into the lumen is not clear. We studied whether trypsin can dissociate Alk-SMase from the mucosa and affect its activity. During luminal perfusion of rat intestine, addition of trypsin to the buffer increased Alk-SMase activity in the perfusate output by about threefold. Treating COS-7 cells transfected with Alk-SMase cDNA with trypsin increased the SMase activity in the medium and reduced that in the cell lysate dose dependently. The appearance of Alk-SMase in the perfusate and culture medium was confirmed by Western blot analysis. The effect of trypsin was blocked by trypsin inhibitor, and neither chymotrypsin nor elastase had a similar effect. We also expressed the full length and COOH-terminal truncated Alk-SMase in COS-7 cells and found that the activity of the full-length enzyme is mainly in the cells, whereas that of the truncated form is mainly in the medium. Both forms were active, but only the activity of the full-length Alk-SMase was enhanced by trypsin. By linking a poly-His tag to the constructed cDNA, we found that the first tryptic site Arg440 upstream of the signal anchor was attacked by trypsin. In conclusion, trypsin cleaves the Alk-SMase at the COOH terminal, releases it from mucosa, and meanwhile enhances its activity. The findings indicate a physiological role of trypsin in SM digestion.

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Role of bile and pancreatic juice in cholesterol absorption and esterification

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1964.206.1.223 ◽

1964 ◽

Vol 206 (1) ◽

pp. 223-228 ◽

Cited By ~ 67

Author(s):

C. R. Borja ◽

George V. Vahouny ◽

C. R. Treadwell

Keyword(s):

Pancreatic Juice ◽

Bile Salts ◽

Intestinal Tract ◽

Dietary Cholesterol ◽

Cholesterol Absorption ◽

Cholesterol Esterase ◽

Thoracic Duct Lymph ◽

Intragastric Administration ◽

Rate Limiting Step

Absence of bile and pancreatic juice in the intestinal tract totally abolished absorption of cholesterol-4-C14 into thoracic duct lymph. Similarly, intestinal cholesterol esterase activity approached zero in animals lacking both bile and pancreatic juice. Intestinal cholesterol esterase could still be demonstrated in animals deprived of pancreatic juice, but which received an infusion or intragastric administration of bile salts. Absorption of cholesterol was shown to occur even in the complete absence of pancreatic juice, provided bile salts were present in the intestinal tract. Some synthesis of cholesterol esterase by the intestinal or reactivation of residual cholesterol esterase in the presence of bile salts is postulated. Thus, pancreatic secretion is not absolutely required for cholesterol absorption, although it has a stimulating effect in the presence of bile salts. This effect is attributed to its cholesterol esterase content. In the presence of bile salts, the process of esterification is postulated to be a rate-limiting step during intestinal absorption of dietary cholesterol.

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Genetic background of cholesterol absorption efficacy. The role of Niemann–Pick C1-like 1 receptor and its genetic variation in lipid metabolism

Orvosi Hetilap ◽

10.1556/oh.2010.28933 ◽

2010 ◽

Vol 151 (34) ◽

pp. 1376-1383 ◽

Cited By ~ 1

Author(s):

Mariann Harangi ◽

István Balogh ◽

János Harangi ◽

György Paragh

Keyword(s):

Genetic Variation ◽

Lipid Metabolism ◽

Genetic Background ◽

Cholesterol Absorption ◽

Niemann Pick

A Niemann–Pick C1-like-1 egy szterolfelismerő domént tartalmazó membránfehérje, amelyet nagy számban expresszálnak csúcsi felszínükön a bélhámsejtek. Az utóbbi évek vizsgálatai azt igazolták, hogy ez a fehérje szükséges a szabad koleszterin bejutásához a bélhámsejtekbe a bél lumenéből. Biokémiai vizsgálatok azt igazolták, hogy a Niemann–Pick C1-like-1-hez kötődik az ezetimib, amely egy hatékony koleszterinfelszívódást gátló szer. A bélből történő koleszterinfelszívódás ütemében és az ezetimibkezelés hatékonyságában tapasztalt egyéni eltérések hátterében felmerült néhány Niemann–Pick C1-like-1 génvariáció oki szerepe.

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Cholesterol absorption in cirrhosis: The role of total and individual bile acid pool size

Gastroenterology ◽

10.1016/0016-5085(81)90253-5 ◽

1981 ◽

Vol 80 (6) ◽

pp. 1428-1437 ◽

Cited By ~ 11

Author(s):

Maurizio Ponz De Leon ◽

Paola Loria ◽

Rossella Iori ◽

Nicola Carulli

Keyword(s):

Bile Acid ◽

Cholesterol Absorption ◽

Pool Size ◽

Bile Acid Pool ◽

Acid Pool ◽

Bile Acid Pool Size

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Role of mesenteric lymphatic system in water absorption from rat intestine in vitro

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1963.204.1.92 ◽

1963 ◽

Vol 204 (1) ◽

pp. 92-96 ◽

Cited By ~ 21

Author(s):

J. S. Lee

Keyword(s):

Water Absorption ◽

Absorption Rate ◽

Lymphatic System ◽

Average Frequency ◽

Rat Intestine ◽

Isolated Segment ◽

Rhythmical Contractions

With an in vitro rat jejunal preparation it was found that at low distention pressures the absorption rate of segments without mesentery are about 40% lower than the rate of those with intact mesentery. The decrease of absorption rate in segments with lacteal ducts sectioned near the gut wall was the same as the rate for those completely devoid of mesentery. Section of blood vessels showed no decrease but rather a slight increase in rate. The mesenteric lymphatic ducts during water absorption in vitro and in vivo showed rhythmical contractions with an average frequency of 10/min. The lymphatic ducts of an isolated mesentery may continue to contract and transport water for a few minutes. The lymphatic pressure of the isolated segment is assumed to be an approximate measure of absorbing force. Epinephrine may augment lymphatic contractility and may also elevate lymphatic pressure. These observations suggest that the mesenteric lymphatics may play a significant role in water transport.

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Role of the Gut in Lipid Homeostasis

Physiological Reviews ◽

10.1152/physrev.00019.2011 ◽

2012 ◽

Vol 92 (3) ◽

pp. 1061-1085 ◽

Cited By ~ 204

Author(s):

Nada A. Abumrad ◽

Nicholas O. Davidson

Keyword(s):

Fatty Acid ◽

Genetic Regulation ◽

Density Lipoprotein ◽

Microsomal Triglyceride Transfer Protein ◽

Cholesterol Absorption ◽

Lessons Learned ◽

Lipid Homeostasis ◽

Integrative View ◽

Familial Hypobetalipoproteinemia

Intestinal lipid transport plays a central role in fat homeostasis. Here we review the pathways regulating intestinal absorption and delivery of dietary and biliary lipid substrates, principally long-chain fatty acid, cholesterol, and other sterols. We discuss the regulation and functions of CD36 in fatty acid absorption, NPC1L1 in cholesterol absorption, as well as other lipid transporters including FATP4 and SRB1. We discuss the pathways of intestinal sterol efflux via ABCG5/G8 and ABCA1 as well as the role of the small intestine in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. We review the pathways and genetic regulation of chylomicron assembly, the role of dominant restriction points such as microsomal triglyceride transfer protein and apolipoprotein B, and the role of CD36, l-FABP, and other proteins in formation of the prechylomicron complex. We will summarize current concepts of regulated lipoprotein secretion (including HDL and chylomicron pathways) and include lessons learned from families with genetic mutations in dominant pathways (i.e., abetalipoproteinemia, chylomicron retention disease, and familial hypobetalipoproteinemia). Finally, we will provide an integrative view of intestinal lipid homeostasis through recent findings on the role of lipid flux and fatty acid signaling via diverse receptor pathways in regulating absorption and production of satiety factors.

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Role of intestinal sterol transporters Abcg5, Abcg8, and Npc1l1 in cholesterol absorption in mice: gender and age effects

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00172.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. G269-G276 ◽

Cited By ~ 54

Author(s):

Li-Ping Duan ◽

Helen H. Wang ◽

Akira Ohashi ◽

David Q.-H. Wang

Keyword(s):

Molecular Mechanisms ◽

Apical Membrane ◽

Cholesterol Absorption ◽

Absorption Efficiency ◽

Biliary Cholesterol ◽

Intestinal Cholesterol Absorption ◽

Gender And Age ◽

Multistep Process ◽

17Β Estradiol

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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