Oxysterols and phytosterols in human health

Cholesterol, initially called cholestérine, was discovered by the French chemist Michel Eugène Chevreul in 1815 during his work on fat related to the soap and candle industry. In 1884, Emile Littré, in his dictionary of medicine, has dubbed cholestérine “cholestérol” (Bourget, 2002). The name of cholesterol originates from the ancient Greek chole (bile) and stereos (solid), because it was initially discovered in its solid form in gallstones in 1758 by another French chemist François Poulletier de La Salle (Schlienger, 2012). Subsequently, during about a century, several studies were carried out on the cholesterol structure and biosynthesis leading to four Nobel prizes. In 1928, Adolf Windaus was awarded Nobel Prize in Chemistry for his research on sterols; in 1964, Konrad Bloch and Feodor Lynen were awarded Nobel Prize in Physiology and Medicine for discovering the mechanism of the cholesterol and fatty acid metabolism; and in 1975, John Cornforth was awarded Nobel Prize in Chemistry for his studies on enzymes allowing him to detail the biosynthesis of cholesterol. Progressively epidemiological and clinical evidence support the hypothesis of an implication of hypercholesterolemia in the initiation and progression of human atherosclerosis and coronaropathy. In 1985, the Nobel Prize of Medicine was discerned to Michael S. Brown and Joseph L. Goldstein for their pioneering work on cholesterol metabolism and Low Density Lipoprotein (LDL) receptor which leads to the discovery of statins, a new generation of hypocholesterolemic drugs, which are now widely used for the treatment of hypercholesterolemia (Goldstein and Brown, 2015). Despite the many studies targeting cholesterol, the diseases associated with cholesterol, in particular, cardiovascular diseases, whose frequency increases with age, are still the leading cause of death in the world according to the World Health Organization. Thanks to the advances in cell biology, analytical biochemistry and molecular biology, it was progressively established that oxidized cholesterol derivatives, namely oxysterols, obtained either from cholesterol by auto-oxidation or by enzymatic catalysis (Smith, 1996, Iuliano, 2011, Mutemberezi et al., 2016) could be involved in many diseases including not only cardiovascular diseases but also ocular diseases (age-related macular degeneration, cataract), neurodegenerative diseases, osteoporosis and some cancers (Brown and Jessup, 1999, Schroepfer, 2000, Björkhem et al., 2006, Zarrouk et al., 2014). Furthermore, it is increasingly possible that some oxysterols are implicated in chronic inflammatory pathologies affecting the gut (Sottero et al., 2017). Several oxysterols modulate specific metabolic pathways and some of them specifically interact with receptors, among them Liver X Receptors (Peet et al., 1998, Kalaany and Mangelsdorf, 2006), which constitute potential pharmacological targets in major diseases. At the moment, a better understanding of the biological activity of oxysterols will open new therapeutic perspectives to pathologies without any efficient treatments (multiple sclerosis, Huntington’s disease, amyotrophic lateral sclerosis, prostate cancer…). In addition to conventional pharmacological strategies, ‘medical bioremediation’ based on the use of microbial enzymes to compensate for missing catabolic functions is a promising approach in order to overcome the insufficiency of oxysterols catabolism (Mathieu et al., 2009). In this context, the 6th European Network for Oxysterol Research (ENOR; http://www.oxysterols.net/) symposium, organized by Prof. Charbel Massaad and his team, held in Paris at the University Paris Descartes from 29 to 30 September 2016, made it possible to have an overview on the implication of oxysterols, but also phytosterols, in human health. This symposium was attended by 87 participants from different European countries (Belgium, Finland, France, Germany, Italy, The Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and UK), but also from outside Europe (Belarus, Brazil, India, Lebanon, Morocco, USA, and Tunisia).