Figure 1.

Production of endogenous triglyceride-rich lipoproteins (TRLs) by the liver. A. Healthy liver (1) ApoB100, one of the largest proteins, is synthesized by hepatocytes in the reticulum (ER) where it is moved along by the concourse of microsomal triglyceride transfer protein (MTTP). (2) Lipidated apo B is moved to the Golgi apparatus by means of COP II (Coat Protein Complex II) vesicles. (3) Finally, very low-density lipoprotein 2 (VLDL2), containing phospholipids and cholesterol besides TG, is secreted into the circulation. B. Liver with excess lipids. (4) TG employed for the synthesis of VLDL may come from re-esterified fatty acids catabolism of remnants or de novo lipogenesis (DNL). DNL implies the synthesis of fatty acids from glycerol and acetyl CoA derived from the metabolism of glucose and fructose. DNL is only 5% (of the total FA synthesis) in normal livers, but in (5) and (6) it reaches 25% when there is insulin resistance, diabetes, and high consumption of sugars or alcohol. Excess fat from DNL, build-up of circulating fatty acids, or liver steatosis is employed to enrich VLDL2 to a much larger particle called VLDL1. As compared to VLDL2, VLDL1 is not larger, but it contains more apoCIII. As we illustrate later, apoCIII is a very potent inhibitor of the catabolism of VLDL, thus promoting hypertriglyceridemia. The prolonged residence time favored by a delayed catabolism promotes the action of hepatic (HL) and endothelial lipase (EL) that ultimately results in the production of small and dense LDL, which is highly atherogenic. (7) We summarize some of the dietary and pharmacological molecules that reduce the production of VLDL1. Unfortunately, but not surprisingly, the pharmacological agents result in the accumulation of TG in the liver, thus producing a fatty liver. The figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license.