Nutrition and Metabolism of Lipids 95

Enterohepatic circulation

The absorption of fat in the small intestine is depen-

dent on the availability of bile acids from biliary

secretions which also contain free cholesterol. Both

bile acids (>95%) and biliary cholesterol are salvaged

by an energy-dependent process in the terminal

ileum. This active process of reabsorption via the

enterohepatic circulation is tightly controlled by a

feedback mechanism that is sensitive to hepatic levels

of cholesterol. Thus, the reabsorption of cholesterol

downregulates the activity of 7-α-hydroxylase in the

liver, shutting down the further production of bile

acids. Substances in the lumen of the gut that are

capable of binding or competing with bound bile

acids, such as naturally occurring plant sterols or

soluble nonstarch polysaccharides (NSPs), prevent

their reabsorption which, in effect, interrupts the

enterohepatic circulation. This depletes the supply of

cholesterol and accelerates the production of bile

acids, depleting the liver of cholesterol (Figure 6.6).

To replenish this loss, liver cells respond by increasing

their uptake of cholesterol from circulating lipopro-

teins in the blood, with the result of a decrease in

blood cholesterol. Interruption of the enterohepatic

circulation helps to explain the cholesterol-lowering

action of some of the earliest known cholesterol-low-

ering drugs, but also such dietary constituents as the

phytosterols (sitosterol and stanol esters) and soluble

fi ber or NSPs. For further details of the control mech-

anism see Section 6.5.

Surface lipids

Free cholesterol

Phospholipid

Protein (apoproteins)

Cholesteryl esters

Triacylglycerols

Core lipids

Figure 6.5 General lipoprotein structure. (Reproduced from Dur-
rington PN. Hyperlipidaemia Diagnosis and Management, 2nd edn.
Elsevier Science, Oxford, copyright 1995 with permission of Elsevier.)

Y

Y

Y

Y

Y

x

Liver cell LDL

LDL

receptors



Dietary cholesterol  bile acids

Anion exchange resins/soluble dietary fiber

Acetate

HMG-CoA reductase

Free cholesterol

7--Hydroxylase

Excreted

in feces

Intestine

>

Figure 6.6 Interruption of the entero-

hepatic circulation. LDL, low-density

lipoprotein; HMG-CoA, 3-hydroxy-3-methyl-

glutaryl-coenzyme A.