Dietary cholesterol absorption

Huggins, K. W., Camarota, L. M., Howies, P. N., and Hui, D. Y. (2003) Pancreatic triglyceride lipase deficiency minimally affects dietary fat absorption but dramatically decreases dietary cholesterol absorption in mice. J. Biol. Chem. 278, 42899-42905. 

During the early 1950s, it was reported that phytosterols lower serum cholesterol (173-175). This effect was appreciated as a possible protection strategy against car-divascular disease risk after the results of several convincing animal and human studies (176-184). Studies have shown that a daily intake of 2-g phytosterol or phytostanol causes 40-50% reduction in the dietary cholesterol absorption, 6-10% reduction in total serum cholesterol, and 8-14% reduction in the semm low-density lipoprotein cholesterol (37, 185-187). 

Stigmasterol is a widely occurring plant steroid that is obtained commercially from soybean oil. jS-Sitostanol (a phytostanol, esters of which inhibit dietary cholesterol absorption) has the same formula except that it is saturated (C5 hydrogen is a). 

The obligatory role of bile acids in the overall process of cholesterol absorption has been largely documented both in animals and in humans. In 1952 Siperstein et al. showed that when labeled cholesterol was given to bile fistula rats virtually no radioactivity was recovered in the thoracic duct lymph in the following 24 hours [32] In keeping with these animal studies Quintao et al. reported that when one patient with primary biliary cirrhosis and complete biliary obstruction was given Ig of cholesterol/day - dissolved in a liquid formula fatty diet - no cholesterol was absorbed[77]. Similarly, dietary cholesterol absorption was significantly lower than normal in patients with advanced liver cirrhosis, who had a marked reduction of total bile acid pool size[88]. 

Regulation of cholesterol absorption by bile acids Role of deoxycholic and cholic acid pool expansion on dietary cholesterol absorption, Ital.J.Gastroenterol., 15 86-93 (1983). 

Ezetimibe (Zetia) is a selective inhibitor of dietary cholesterol absorption. In addition to this decreased cholesterol absorption leads to an increase in LDL-cholesterol uptake into cells, thus decreasing levels in the blood plasma (Rossi S, 2006). 

Reduction of LDL cholesterol levels by inhibiting dietary cholesterol absorption... 

Ezetimibe is the first drug in a new class of agents referred to as cholesterol absorption inhibitors. Ezetimibe blocks biliary and dietary cholesterol as well as phytosterol (plant sterol)... 

Hauser, H. et al. (1998). Identification of a receptor mediating absorption of dietary cholesterol in the intestine. Biochemistry 37(51) 17843-17850. 

The intestinal absorption of dietary cholesterol esters occurs only after hydrolysis by sterol esterase steryl-ester acylhydrolase (cholesterol esterase, EC 3.1.1.13) in the presence of taurocholate [113][114], This enzyme is synthesized and secreted by the pancreas. The free cholesterol so produced then diffuses through the lumen to the plasma membrane of the intestinal epithelial cells, where it is re-esterified. The resulting cholesterol esters are then transported into the intestinal lymph [115]. The mechanism of cholesterol reesterification remained unclear until it was shown that cholesterol esterase EC 3.1.1.13 has both bile-salt-independent and bile-salt-dependent cholesterol ester synthetic activities, and that it may catalyze the net synthesis of cholesterol esters under physiological conditions [116-118], It seems that cholesterol esterase can switch between hydrolytic and synthetic activities, controlled by the bile salt and/or proton concentration in the enzyme s microenvironment. Cholesterol esterase is also found in other tissues, e.g., in the liver and testis [119][120], The enzyme is able to catalyze the hydrolysis of acylglycerols and phospholipids at the micellar interface, but also to act as a cholesterol transfer protein in phospholipid vesicles independently of esterase activity [121],... 

Beynen. The hypercholesterolemic effect of dietary coconut fat versus com CN116 oil in hypo- or hyperresponsive rabbits is not exerted through influencing cholesterol absorption. Lipids 1991 CN117... 

Cholesterol Transport Protein Inhibitor Ezetimibe is the first hypolipidemic agent to act by blocking the absorption of dietary cholesterol at the intestinal level. It represents a novel treatment option for patients with hypercholesterolemia, alone or in combination with statins (Figure 8.60). 

Ezetimibe is a selective inhibitor of intestinal absorption of cholesterol and phytosterols. A transport protein, NPC1L1, appears to be the target of the drug. It is effective even in the absence of dietary cholesterol because it inhibits reabsorption of cholesterol excreted in the bile. 

Plant sterols Commercially available margarines containing hydrogenated plant sterols and sterol esters (predominantly sitostanol esters), when used in place of regular margarine, can reduce LDL plasma cholesterol concentrations. The mechanism by which these compounds lower LDL cholesterol concentrations is to inhibit intestinal absorption of dietary cholesterol and cholesterol secreted into the bile. 

Dietary cholesterol, together with triacylglycerols, is absorbed from the intestinal tract and enters the large lipoprotein chylomicrons (see Fig. 21-1). Absorption of cholesterol is incomplete, usually amounting to less than 40% of that in the diet. Absorption requires bile salts and is influenced by other factors.186 As it is needed cholesterol is taken from the plasma lipoproteins into cells by endocytosis. Much of the newly absorbed cholesterol is taken up by the liver. The liver also secretes cholesterol, in the form of esters with fatty acids, into the bloodstream. 

Burnett et al. [16] have reported monocyclic (3-lactam I as a potent cholesterol absorption inhibitor in vivo, and this can inhibit the absorption of dietary... 

The two significant sources of cholesterol in body are endogenously synthesized cholesterol and exogenous or dietary cholesterol. Efforts to inhibit the absorption of dietary cholesterol have primarily focused on the inhibition of ACAT, a major enzyme associated with cholesterol esterification. Inhibition of this enzyme blocks the absorption of intestinal cholesterol and may also inhibit cholesteryl ester deposition in the vascular wall in the form of fatty streaks associated with atherosclerotic plaque. 

Does Citrus Pectin Bind Bile Salts A possible mechanism by which dietary pectin may cause lowering of cholesterol levels in rats has been reported (1 9). In these in vitro studies, pectin was found to inhibit the transport of taurocholic acid from everted sacs of rat intestine. The absorption of labelled cholesterol was depressed by the addition of 5% pectin to the diet as evidenced by increased excretion of labelled cholesterol and diminished cholesterol deposition in the liver. It was concluded from these studies that pectin lowers cholesterol levels in cholesterol-fed rats primarily by binding bile salts and, consequently, by impairing cholesterol absorption. Results similar to those obtained with dietary pectin and described have also been reported for other non-nutritive substances such as guar gum, psyllium seed colloid and seruglucan (20). 

There are several ways pectin could reduce serum cholesterol. In studies with human subjects, fecal excretion of bile acids, fatty acids, and total steroids increased when subjects were fed 15-40 g/day of pectin (58, 63, 64). Since pectin usually lowers serum cholesterol only when cholesterol is present in the diet, it seems that pectin might act by reducing cholesterol absorption. Several groups have found that in rats dietary... 

He suggested that the effect may be due to an interference in enterohepatic circulation and/or an inhibition of the absorption of dietary cholesterol. The latter hypothesis is likely the more accurate explanation, as we found no other evidence of an interference in enterohepatic circulation, such as changes in serum bilirubin levels. 

This article focuses on specific dietary components—whether naturally occurring or added as food ingredients—known to interfere with the mechanisms of cholesterol absorption. An overview of cholesterol absorption is provided and emphasizes the critical role of bile acids and micelle formation in solubilizing cholesterol for transport to the brush border membrane of enterocytes. Where applicable, information is also included about commercial food ingredients that are specifically used as cholesterollowering agents. 

Cholesterol enters the small intestine from two sources the diet and bile (Figure 1). Dietary intake of cholesterol is about 300 mg/day (Briefel and Johnson, 2004 Ishinaga et al., 2005 Valsta et al., 2004), whereas the bile contributes 800-1400 mg/day (Duane, 1993 Grundy and Metzger, 1972). The liver not the diet—is therefore the primary source of cholesterol available for absorption, a point that is often underappreciated. Consequently, therapies that block cholesterol absorption are effective at lowering LDL cholesterol mainly because they prevent the reabsorption of endogenous... 

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