Sterols are lipophilic compounds that can be classified into phytosterols, zoosterols and mycosterols depending on their natural origin (plant, animal and fungal, respectively). Among zoosterols, cholesterol, which can however be synthesized by some plants, is the most well known. In humans, cholesterol is produced endogenously and can be also introduced through the diet. In the blood, cholesterol is transported by lipoproteins, and the accumulation of low density lipoproteins (LDL) in the arterial wall favor the formation of the atherosclerotic plaque, leading to various cardiovascular diseases. In this process, the oxidation of LDL by reactive oxygen and nitrogen species (ROS and RNS) produced by activated resident macrophages and foam cells favors both LDL oxidation and cholesterol oxidation. This local overproduction of ROS and RNS contributes to the auto-oxidation of cholesterol and to the formation of oxysterols (cholesterol oxidation products), mainly 7-ketocholesterol (7KC), also named 7-oxo-cholesterol, and 7β-hydroxycholesterol (7β-OHC) and 5,6-epoxycholesterols. In addition to cardiovascular diseases, these oxysterols, mainly formed by auto-oxidation of cholesterol, are also associated with chronic and aged-related diseases such as neurodegenerative, eye and bowel diseases. Diet and cooking habits are also important sources of cholesterol and oxysterols. While dietary cholesterol and oxysterols are rapidly metabolized by the liver into bile acids, the transient increase of these molecules in the plasma can favor their accumulation in the arterial wall. In addition, high oxysterol content in foods could also favor bowel diseases. More recently, due to the rupture of RedOx homeostasia in aging and major neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s diseases, and multiple sclerosis (MS), a potential role of 7KC and 7β-OHC is suspected in this context as well as in cancer. Besides the contribution of oxysterols formed by auto-oxidation and deriving from the diet, several other oxysterols formed enzymatically play major roles in the pathophysiology of numerous diseases. This is the case of Dendrogenin A (DDA), 5,6-epoxycholesterols and 27-hydroxycholesterol in cancer, of 24S-hydroxycholesterol in neurodegeneration (mainly AD), and of 25-hydroxycholesterol and some of its metabolites in MS. Several cytoplasmic and nuclear receptors associated with oxysterol-biological activities have also been identified and the most famous are oxysterol binding proteins (OSBPs) and LXRs receptors. The latter is involved in the control of numerous biological processes (i.e. cancerization and myelin sheath synthesis). In this context, the 8th European Network for Oxysterol Research (ENOR;http://www.oxysterols.net/) Symposium (“Oxysterols and Sterols: from Lipidomics to Food Sciences”), held in Bologna from 20 to 21 September 2018, made it possible to have an overview on the implication of sterols and their oxidation products in human health.
Oxysterols and sterols: From lipidomics to food sciences / M.T. Rodriguez-Estrada, V. Cardenia, M. Poirot, L. Iuliano, G. Lizard. - In: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY. - ISSN 0960-0760. - STAMPA. - 196:(2020), pp. 1-2. [10.1016/j.jsbmb.2019.105515]
Oxysterols and sterols: From lipidomics to food sciences
M. T. Rodriguez-Estrada;
2020
Abstract
Sterols are lipophilic compounds that can be classified into phytosterols, zoosterols and mycosterols depending on their natural origin (plant, animal and fungal, respectively). Among zoosterols, cholesterol, which can however be synthesized by some plants, is the most well known. In humans, cholesterol is produced endogenously and can be also introduced through the diet. In the blood, cholesterol is transported by lipoproteins, and the accumulation of low density lipoproteins (LDL) in the arterial wall favor the formation of the atherosclerotic plaque, leading to various cardiovascular diseases. In this process, the oxidation of LDL by reactive oxygen and nitrogen species (ROS and RNS) produced by activated resident macrophages and foam cells favors both LDL oxidation and cholesterol oxidation. This local overproduction of ROS and RNS contributes to the auto-oxidation of cholesterol and to the formation of oxysterols (cholesterol oxidation products), mainly 7-ketocholesterol (7KC), also named 7-oxo-cholesterol, and 7β-hydroxycholesterol (7β-OHC) and 5,6-epoxycholesterols. In addition to cardiovascular diseases, these oxysterols, mainly formed by auto-oxidation of cholesterol, are also associated with chronic and aged-related diseases such as neurodegenerative, eye and bowel diseases. Diet and cooking habits are also important sources of cholesterol and oxysterols. While dietary cholesterol and oxysterols are rapidly metabolized by the liver into bile acids, the transient increase of these molecules in the plasma can favor their accumulation in the arterial wall. In addition, high oxysterol content in foods could also favor bowel diseases. More recently, due to the rupture of RedOx homeostasia in aging and major neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s diseases, and multiple sclerosis (MS), a potential role of 7KC and 7β-OHC is suspected in this context as well as in cancer. Besides the contribution of oxysterols formed by auto-oxidation and deriving from the diet, several other oxysterols formed enzymatically play major roles in the pathophysiology of numerous diseases. This is the case of Dendrogenin A (DDA), 5,6-epoxycholesterols and 27-hydroxycholesterol in cancer, of 24S-hydroxycholesterol in neurodegeneration (mainly AD), and of 25-hydroxycholesterol and some of its metabolites in MS. Several cytoplasmic and nuclear receptors associated with oxysterol-biological activities have also been identified and the most famous are oxysterol binding proteins (OSBPs) and LXRs receptors. The latter is involved in the control of numerous biological processes (i.e. cancerization and myelin sheath synthesis). In this context, the 8th European Network for Oxysterol Research (ENOR;http://www.oxysterols.net/) Symposium (“Oxysterols and Sterols: from Lipidomics to Food Sciences”), held in Bologna from 20 to 21 September 2018, made it possible to have an overview on the implication of sterols and their oxidation products in human health.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
