The role of fat tissue in the cholesterol lowering and the pleiotropic effects of statins – statins activate the generation of metabolically more capable adipocytes

Abstract

Statins have very important influences on adipocyte physiology, particularly via their effects on sterol regulatory element binding proteins (SREBPs), which are extremely important transcription factors for the regulation of adipocyte physiology. SREBP-1c activation in fat cell by the cytosolic cholesterol deprivation through HMG-reductase inhibition is responsible for most of the beneficial effects of statins. Glucose and lipid excess, and oxidative overload coming with energy dense nutrition, which might be deleterious, can be removed from the circulation by adipo-lipogenetic enhancement through the activated SREBP-1c. SREBP-1c causes formation of new small and competent adipocytes, which are insulin and leptin sensitive. Thus, adipocytes gain the ability of fat storing, and much more importantly, fat-burning machines. Statins already have a large and growing number of indications in the treatment of atherovascular diseases. General mechanism for the action of statins is their inhibitory effects on 3-hydroxy 3-methyl glutaryl CoA reductase, which is the rate-limiting enzyme in cholesterol biosynthesis, particularly in the liver. Recently, the beneficial effects of statins beyond their cholesterol lowering, which are called pleiotropic effects, have been the focus of great attention. Certain characteristics of the statin molecule itself have been proposed to explain these effects. Adipocytes are in the very heart of metabolic regulations. Therefore, the important elements of the pleiotropic effects of statins occur through executive improvements on impaired adipocyte functions by the activation of SREBP-1c.