Facts about Fats: New Insights into the Role of Lipids in Metabolism Disease and Therapy

摘要

Although initially regarded as a passive system to store energy, lipids are now considered to play crucial, structural and functional roles in almost all the biological processes involved in the regulation of physiological and pathological conditions. For instance, they are pivotal constituents of cell membranes, where they essentially contribute to the assembly of the bilayer configuration. Lipid species are not uniformly distributed in cell membranes, as they are mainly concentrated in specialized sphingolipid- and cholesterol-rich domains called lipid rafts and caveolae, which serve as a matrix for the attachment and the interaction of several proteins implicated in membrane-initiating signal transduction pathways [1]. Besides the involvement in the organization of membrane domains, lipids may influence numerous cellular processes by directly participating as both primary and secondary messengers. In recent decades, lipids derived from both dietary sources and endogenous biosynthesis gained considerable clinical relevance for their implications in a plethora of human diseases. Hyperlipidemia often results in a premature and increased risk of cardiovascular diseases [2]. Increasing evidence highlights that the metabolic reprogramming of cancer cells also involves many lipid compounds, such as fatty acids and cholesterol, which contribute to key oncogenic functions [3,4]. Furthermore, a variety of experimental and clinical studies demonstrated that lipids, particularly cholesterol, play essential roles in brain physiology [5]. Thus, it is not surprising that numerous neurological and neurodegenerative disorders are often accompanied by misbalances in lipid homeostasis [6].