Statins-induced inhibition of the cholesterol synthesis in liver and very low-density lipoproteins. Statins, fatty acids and insulin resistance

Abstract

In liver statins block synthesis of the specific cholesterol (CH) pool, which is produced de novo by hepatocytes for the monolayer of polar lipids located at the surface of the forming very low-density lipoproteins (VLDL). By diminishing of unetherified CH content in the monolayer the statins activate hydrolysis of triglycerides into the VLDL, generation of low-density lipoproteins (LDL), and their absorption by the cells through the apoB-100 receptors. Activation of the LDL absorption leads to recovery of functional activity of essential polyene fatty acids (poly-FA) by statins. Poly-FA, fibrates, and glitazones form an effective oleic-type metabolism in the cells, where the mitochondria oxidize oleic FA, primarily. Statins do not activate oxidation in peroxisomes, while inhibit stearyl-CoA-desaturase, by which they develop the less effective palmitic type of FA metabolism in the cells, when the mitochondria oxidize palmitic acid, mainly. To synthesize optimal ATP quantity the FA pool from the exogenic triglycerides hydrolysis is not enough; the FA stored in adipocytes have to be used, which is the reason of statins-induced development of insulin resistance. Phylogenetically, LDL and VLDL are different in function, i.e. VLDL transport the FA to the cells in the form of triglycerides, while LDL transport the FA in the form of the ethers with CH. Statins normalize absorption of essential poly-FA by the cells, which possess a physiological activity called pleotropic.