Pancreatic juice contains two enzymes crucial for fat digestion. One of these enzymes is phospholipase A2, which breaks down phospholipids found in cell membranes. To prevent toxicity in the absence of dietary substrates, it is secreted as an inactive pro-form that becomes active only in the small intestine. Additionally, pancreatic juice contains a cholesterol esterase that breaks down cholesterol esters, fat-soluble vitamin esters, and triglycerides. Unlike lipase, this enzyme requires bile acids for activity. Interestingly, it is related to an enzyme found in breast milk that aids in neonatal lipolysis.

During lipolysis, the lipid droplet's products are extracted and transferred into a lamellar phase and then into mixed micelles. Bile acids, which are amphipathic, protect the hydrophobic regions of the lipolytic products from water and present their hydrophilic faces to the aqueous environment. Micelles are soluble and significantly increase lipid solubility in the intestinal contents. This facilitates the diffusion of molecules like fatty acids to the absorptive epithelial surface. While micelles are not essential for triglyceride absorption due to the large surface area of the small intestine and the solubility of triglyceride products, they are necessary for the absorption of cholesterol and fat-soluble vitamins. If luminal bile acid concentrations fall below the critical micellar concentration, fat-soluble vitamin deficiency may occur, although fat malabsorption is not typically observed in patients with insufficient bile acid output.

The uptake of fat digestion products is believed to occur easily due to their lipophilicity. However, recent evidence suggests that specific membrane transporters may also regulate their uptake. Microvillus membrane fatty acid–binding protein (MVM-FABP) facilitates the uptake of long-chain fatty acids across the brush border. Additionally, Niemann-Pick C1–like 1 (NPC1L1) has been identified as an uptake pathway for cholesterol in enterocytes and may be a therapeutic target for hypercholesterolemia. Nonetheless, cholesterol uptake is relatively inefficient as it, along with plant sterols, can be actively transported out of enterocytes into the cytosol by a complex of two ATP-binding cassette (ABC) transporters called ABC G5 and G8. Lastly, various aquaglyceroporins transport the glycerol backbone of triglycerides into intestinal epithelial cells.
Pancreatic juice also contains two additional enzymes that are important in fat digestion. The first of these is phospholipase A2, which hydrolyzes phospholipids such as those present in cell membranes. Predictably this enzyme would be quite toxic in the absence of dietary substrates, and thus it is secreted as an inactive pro-form that is activated only when it reaches the small intestine. Furthermore, pancreatic juice contains a relatively nonspecific cholesterol esterase that can break down esters of cholesterol, as its name implies, as well as esters of fat-soluble vitamins and even triglycerides. Interestingly this enzyme requires bile acids for activity (contrast with lipase, discussed earlier), and it is related to an enzyme produced in breast milk that plays an important role in lipolysis in neonates.
As lipolysis proceeds, the products are abstracted from the lipid droplet, first into a lamellar (membrane) phase and subsequently into mixed micelles composed of lipolytic products as well as bile acids. The amphipathic (meaning they have both a hydrophobic and hydrophilic face) bile acids serve to shield the hydrophobic regions of lipolytic products from water while presenting their own hydrophilic faces to the aqueous environment (
Fig. 30.15 ). Micelles are truly in solution and thus markedly increase lipid solubility in the intestinal contents. This increases the rate at which molecules such as fatty acids diffuse to the absorptive epithelial surface. Nevertheless, given the very large surface area of the small intestine and the appreciable molecular solubility of the products of triglyceride hydrolysis, micelles are not essential for the absorption of triglyceride. Thus patients who have insufficient output of bile acids (caused, for example, by a gallstone that obstructs bile output) do not normally show fat malabsorption. On the other hand, cholesterol and the fat-soluble vitamins are almost totally insoluble in water and accordingly require micelles to be absorbed even after they have been digested. Thus if luminal bile acid concentrations fall below the critical micellar concentration, patients can become deficient in fat-soluble vitamins.
•Fig. 30.15 Schematicdepictionofbileacids(A)andmixedmicelles(B).Bileacidsinsolutionareamphipathic.Mixedmicellesarecylindricalassemblagesofbileacidswithotherdietarylipids.
Uptake of Lipids and Subsequent Handling
The products of fat digestion are believed to be capable of crossing cell membranes readily because of their lipophilicity. However, recent evidence suggests that their uptake may alternatively or additionally be regulated via the activity of specific membrane transporters. A microvillus membrane fatty acid–binding protein (MVM-FABP) provides for the uptake of long-chain fatty acids across the brush border. Likewise, Niemann-Pick C1–like 1 (NPC1L1) has recently been identified as an uptake pathway for cholesterol in enterocytes and may be a therapeutic target in patients who suffer from pathological increases in circulating cholesterol (hypercholesterolemia). However, uptake of cholesterol overall is relatively inefficient because this molecule, along with plant sterols, can also be actively effluxed from enterocytes back into the cytosol by a heterodimeric complex of two ATP-binding cassette (ABC) transporters termed ABC G5 and G8. Finally, the glycerol backbone of triglycerides may be transported into intestinal epithelial cells by a number of different aquaglyceroporins.