There are two ways to increase the amount of cholesterol in LDL. One is to increase the amount of cholesterol secreted to begin with; the other is to decrease the rate of disposal of cholesterol once it’s been created (which is apparently what happens when we eat saturated fat). Either method will eventually result in elevated LDL cholesterol. Joseph Goldstein and Michael Brown worked out the details of the clearance-and-disposal mechanism in the 1970s, and this work won them the Nobel Prize.

As for secretion, the key point is that most low-density lipoproteins, LDL, begin their lives as very low-density lipoproteins, VLDL. (This was one implication of the observation that both LDL and VLDL are composed of the same apo B protein, and it was established beyond reasonable doubt in the 1970s.) This is why VLDL is now commonly referred to as a precursor of LDL, and LDL as a remnant of VLDL. If the liver synthesizes more cholesterol, we end up with more total cholesterol and so more LDL cholesterol, although apparently not more LDL particles. If the liver synthesizes and secretes more VLDL, we will also end up with more LDL cholesterol but we have more LDL particles as well, and they’ll be smaller and denser.

This process is easier to understand if we picture what’s actually happening in the liver. After we eat a carbohydrate-rich meal, the bloodstream is flooded with glucose, and the liver takes some of this glucose and transforms it into fat—i.e., triglycerides—for temporary storage. These triglycerides are no more than droplets of oil. In the liver, the oil droplets are fused to the apo B protein and to the cholesterol that forms the outer membrane of the balloon. The triglycerides constitute the cargo that the lipo-proteins drop off at tissues throughout the body. The combination of cholesterol and apo B is the delivery vehicle. The resulting lipoprotein has a very low density, and so is a VLDL particle, because the triglycerides are lighter than either the cholesterol or the apo B. (In the same way, the more air in the hold of a ship, the less dense the ship and the higher it floats in the water.) For this reason, the larger the initial oil droplet, the more triglycerides packaged in the lipoprotein, the lower its density.