Retinol metabolism in hepatic stellate cells: a new vision

Abstract

Vitamin A (all-trans-retinol) or its derivatives are involved in many physiological processes ranging from vision to cells differentiation. In mammals retinol is stored as retinyl ester (RE) and the liver is the major site for RE storage in the body. The liver is made of various cell types and REs are predominantly stored in hepatic stellate cells (HSCs). Under physiological conditions these cells play an important role in vitamin A homeostasis. One important characteristics of HSCs are their RE rich lipid droplets (LDs). In fact approximately 35% of the neutral lipid core of this droplet is RE, a percentage which strongly depends on the amount of dietary vitamin A. Under pathological conditions, like hepatic fibrosis, HSCs undergo both metabolic and morphological changes. The morphology of HSCs changes from a star-shaped stellate cell to that of a (myo-) fibroblast. During this trans-differentiation the HSCs lose their vitamin A-rich lipid droplets and start synthesizing extracellular matrix components. In this dissertation various enzymes and metabolic pathways related to REs storage was studied in cell lines and transgenic mice. Advance technique in lipidomics was adapted in this dissertation to elucidate the LD dynamics in HSCs in relation to Vitamin A storage metabolism.