If you eat like the average American, somewhere around forty percent of your dietary calories probably come from fats (in my case, it’s more like 70 percent). As we’ve seen, the job of the lipoproteins is to make sure all that nutrition gets distributed correctly. Lipoproteins contain some cholesterol, but mostly they contain triglycerides, other fatty nutrients (like lecithin, choline, essential fatty acids, and phospholipids), varying amounts of fat-soluble vitamins, and retinoids—all wrapped inside a protein coat.
After your food is broken down by enzymes in the intestine, the fat and most other nutrients get absorbed into intestinal cells (called enterocytes). Here, fat and fat-soluble nutrients are prepared for circulation through the bloodstream. Since fat particles won’t dissolve in blood, the intestinal cells wrap these tiny balls of fatty nutrients in a protein coat. Lipoproteins made in the intestine are called a chylomicrons. Other tissues that participate in the lipid cycle make other types of lipoproteins, all with the same general design: a blob of fat wrapped in protein.
Cells that make lipoproteins don’t throw just any old protein coating over the fats, kick the little particle out into circulation and say, “Good luck!” The cells of our bodies must be able to recognize lipoproteins as sources of fatty nutrients. So the protein coating (made of apoproteins) also serves as a kind of barcode describing the particle’s origin and contents. When released into circulation, the wonderfully designed apoproteins also function like little handles, enabling hungry cells to grab the lipoprotein particle as it floats by.
As with any package delivery service, the accuracy of this labeling system is critical to the success of the whole delivery process. If anything were to damage the label (we’ll return to this idea soon), the lipoprotein would fail to carry out its function, and the whole system would be thrown out of whack.
After the packaged lipoprotein leaves an intestinal cell, it travels through the bloodstream for several hours, completing many circuits. As it floats along, it deposits its fatty nutrients into the tissues that need them most.
Hungry tissues get fed by signaling endothelial cells lining their smallest blood vessels to place special proteins on their surface, which act like tiny fishing rods set to snag lipoproteins as they float
by. Once snagged, the particle may unload some of its payload into the endothelial cell or, alternatively, the endothelial cell may open up a tunnel-like structure right through its center to allow the lipoprotein to pass from the bloodstream, through the endothelial cell, and directly into the hungry tissues.
Hours after a meal, the amount of fat in circulation drops as lipoproteins either exit the circulation or give up their fat and shrink (gradually increasing in density as they travel). Eventually, the liver picks up the shrunken, high-density remnants and sorts through the contents to recycle anything useful while discarding any waste. Unwanted or damaged fats exit by way of the bile system back into the intestinal tract for disposal.
The lipid cycle can take any of several different routes. Fats can enter the circulation by way of the intestine (as chylomicrons) or by way of the liver, or even by way of the skin. There are actually multiple points of entry. Even the brain may participate. Fats can exit the cycle by being transported into a hungry cell, or by being exported out of the body through the liver’s bile system.
The liver is like a transfer station. It sorts through the incoming lipoproteins to separate the good fats from the bad. When it has collected enough good fats, the liver fashions its own lipoproteins (called VLDL, for Very LDL), complete with new identifying labels, and sends them back into the bloodstream again. These particles go through another arm of the cycle, following the same series of steps, delivering cargo piecemeal or transporting to a final destination intact. Those particles that deliver cargo piecemeal eventually get small enough to be picked up by the liver again, where they will be disassembled and their fats either discarded or recycled once more.
One loop of the lipid cycle starts in the intestine and distributes lipids you just ate. Another starts in the liver and distributes lipoproteins your liver made. And a third loop starts in the periphery—that is, the rest of the body—and distributes lipoproteins made by the skin, brain, and other organs. Each of the three sources (intestine, liver, and periphery) manufactures its own brand of lipoproteins complete with its own proprietary labels.
When everything works properly, your arteries stay wide-open, pretty pink, and clean. But when fats don’t get delivered properly, they pile up in the bloodstream, damaging epithelial cells and giving arteries a yellowish, irregular, lumpy appearance that is conspicuously unhealthy (see Figure 3).
Obviously, this intricate and ancient internal postal system is amazing and complex. And I don’t mean to imply, by describing it to you, that I know everything about the way it works. I don’t. But let me tell you a secret: neither do the drug manufacturers who tell us we need to get our LDL numbers down, and they have just the pill to do it. As with any system of the body, you don’t need to fully understand it to be able disrupt it with powerful chemicals. Which is exactly what cholesterol- lowering drugs do.