Study of the effects of oxidized derivatives of linoleic acid on astrocyte lipid composition and accumulation of lipid droplets

• Grant number: 21/09326-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2021
• Effective date (End): September 30, 2022
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Sayuri Miyamoto
• Grantee: Gabriela Ernandes Humizava Poiato
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

Linoleic acid (LA) is a polyunsaturated fatty acid (PUFA) of the omega-6 family that can be found in many foods and vegetable oils. Due to the growth in soy production and consumption of processed foods, LA consumption has grown exponentially since the beginning of the 20th century. Once obtained from the diet, LA can be stored in lipid2 droplets in the form of triacylglycerol or cholesteryl esters, serve as an energy source when undergoing ²-oxidation reactions, or be used as a precursor to other omega-6 PUFAs. Furthermore, LA can undergo oxidation by enzymatic and non-enzymatic pathways involving reactive oxygen species (ROS), generating several oxidized metabolites (OXLAM), such as hydroperoxides, hydroxides, and ketones. Among these, 13-hydroxy-octadecadienoic acid (13-HODE) and 9-hydroxy-octadecadienoic acid (9-HODE) stand out, which have been related to some pathological conditions, such as Alzheimer's and amyotrophic lateral sclerosis. In general, neurodegenerative diseases share several cellular changes, such as an imbalance between the production of reactive species and antioxidant defenses, resulting in the oxidation of biomolecules such as lipids. Such redox imbalance can lead to several cellular alterations that include chronic inflammation and alterations in the lipid metabolism of glial cells, such as astrocytes. It is hypothesized that an increase in the concentration of Hodes, resulting from the oxidation of LA, constantly activates PPARy, contributing to the accumulation of fatty acids. This increase in concentration possibly occurs due to the high levels of ROS generated mainly by the induction of mitochondrial damage that happens in neurodegenerative diseases. Therefore, this project aims to analyze the lipid composition (lipidoma) of astrocytes treated with oxidized LA species synthesized in vitro, in addition to investigating the effect of these oxidized fatty acids on the formation of fat droplets (lipid droplets) and possible changes in lipid metabolism and mitochondrial in these cells. (AU)