Absorption Transport and Storage Cholesterol Absorption

Cholesterol in the intestinal lumen typically consists of one-third dietary cholesterol and two-thirds biliary cholesterol. The average daily diet contains 300-500 mg of cholesterol obtained from animal

Cholecalciferol see Vitamin D: Physiology, Dietary Sources and Requirements; Rickets and Osteomalacia

Table 1 Average cholesterol metabolism values for a 70-kg adult

Cholesterol pools and flux Mass

Table 1 Average cholesterol metabolism values for a 70-kg adult

Cholesterol pools and flux Mass

Cholesterol pool (70-kg adult)

160 g

Plasma cholesterol pool

8g

Dietary cholesterol intake

300 mg/day

Absorption (average 60%)

180 mg/day

Synthesis (12mg/kg/day)

840 mg/day

Total cholesterol input

1020 mg/day

Bile acid synthesis (= fecal excretion)

250 mg/day

Neutral steroid excretion

770 mg/day

products. The bile provides an additional 8001200 mg of cholesterol throughout each day as gallbladder contractions provide a flow of bile acids, cholesterol, and phospholipids to facilitate lipid digestion and absorption. Dietary cholesterol is a mixture of free and esterified cholesterol, whereas biliary cholesterol is nonesterified and is introduced into the small intestine as a cholesterol-bile salt-phospholipid water-soluble complex. The only other source of intraluminal cholesterol is mucosal cell cholesterol, derived from either sloughed muco-sal cells or cholesterol secreted by the mucosal cells into the intestinal lumen. Measurements of exogenous and endogenous cholesterol absorption in humans indicate that there is probably very little direct secretion of newly synthesized cholesterol from mucosal cells into the intraluminal contents.

Cholesterol absorption occurs primarily in the duodenum and proximal jejunum of the small intestine and is dependent on the presence of bile salts. In the absence of bile secretion, or in the presence of bile acid-binding resins, there is virtually no intestinal absorption of cholesterol. On average, humans absorb 50-60% of the intestinal contents of cholesterol, but there is a large interindividual variance in absorption, with values ranging from as low as 20% to as high as 80%. Intestinal transit time is related to cholesterol absorption, with slower transit times resulting in higher fractional absorption rates. Dietary factors that affect the relative percent absorption of cholesterol include the total mass of dietary cholesterol, the concentration of plant sterols in the diet, and the type and amount of dietary fiber. Studies suggest that the ratio of polyunsaturated to saturated fat (P:S) in the diet has little effect on cholesterol absorption rates in humans, nor does the amount of dietary fat.

Two interesting, and as yet undefined, aspects of cholesterol absorption are that it decreases as the mass of cholesterol increases above an intake of 1500 mg per day, and that the fractional absorption below this level is relatively constant for an individual. For example, at a daily cholesterol intake of

800 mg a subject may absorb 60% or 480 mg per day, whereas at a daily intake of 400 mg the absorption remains at 60%, equaling 240 mg per day absorbed. The quandary is that if the system can accommodate absorption of 480 mg at the high cholesterol intake, then why is the amount absorbed 240 mg at the low intake? Clearly, the upper value of cholesterol absorption is achievable, yet at the lower intake level the absorption rate stays at a fixed fractional value. The mechanisms controlling this aspect of cholesterol absorption have not been defined.

Experimental evidence indicates that biliary cholesterol and dietary cholesterol are absorbed equally; however, the pattern of exogenous and endogenous cholesterol absorption differs along the length of the intestinal lumen. Dietary cholesterol enters the small intestine solubilized in the oil phase of the stomach digest, whereas the binary cholesterol enters in the micelle phase of the bile. This differential distribution results in a greater absorption of biliary cholesterol in the upper portion of the small intestine, with dietary cholesterol absorption increasing as the oil phase of the intestinal contents are hydrolyzed. As the oil phase is reduced, dietary cholesterol moves from the oil phase to the aqueous micelle phase and becomes available for absorption. In the case of cholesteryl esters in the diet, it is necessary that the esters are hydrolyzed by pancreatic cholesterol esterase (CEase) before the cholesterol is available for absorption. Pancreatic CEase requires the presence of bile salts for activity and may play a key role in the actual absorption process.

The process, and selectivity, of sterol absorption involves a complex interplay of regulated transporters, transporting sterols into and out of the entero-cyte, and the assembly and secretion of chylomicrons into the lymph. The enterocyte takes up both cholesterol and phytosterols from the intestinal lumen by what appears to be a common sterol transporter or permease in the brush border membrane. Preliminary studies suggest that the Neiman-Pick C1 like 1 (NPC1L1) protein is involved in this process. Once the sterols enter the enterocyte, the ATP binding cassette (ABC) hemitransporters ABCG5 and ABCG8 function in the apical excretion of sterols back into the intestinal lumen. The selectivity of this process accounts for the higher absorption rates of cholesterol (50-60%) compared to the phytosterols, which are very poorly absorbed. Loss of ABCG5/G8 function results in excessive absorption of both cholesterol and phytosterols. Studies in mice have shown that ABCG5/G8 are expressed primarily in the liver and intestine, are coordinately upregulated at the transcriptional level by dietary cholesterol intake, and require the liver X receptor-a (LXR-a), a nuclear receptor that regulates the expression of a number of key genes involved in lipid metabolism.

Evidence is accumulating that the fractional cholesterol absorption rates are regulated by one or more genetic determinants. The apolipoprotein (apo) E phenotype has a significant effect on fractional cholesterol absorption and appears to play a major role in determining the plasma lipoprotein response to changes in dietary cholesterol intake. Men with the apoE4 allele have a high cholesterol absorption rate, whereas those with the apoE2 allele have a low cholesterol absorption efficiency. The absorption values for the more common apoE3/3 fall between the apoE2 and apoE4 patterns. Polymorphisms of the apolipoprotein A-IV and of the low-density lipoprotein (LDL) receptor gene have also been related to differences in fractional cholesterol absorption. These genetic variants affecting cholesterol absorption no doubt play a significant role in determining an individual's fractional absorption of cholesterol as well as accounting for much of the heterogeneity of plasma lipid responses to changes in dietary cholesterol intakes.

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Responses

  • elanor
    How much cholesterol in 70kg human?
    2 years ago

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