Study of fatty acids transport across the blood brain barrier in iron deficiency condition.

• Grant number: 22/16448-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2023
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Kil Sun Lee
• Grantee: Luiza Travaglini Manechini
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/12605-8 - Development of brain-on-a-chip microplataforms for in vitro modeling of the central nervous system, AP.TEM

Abstract

Obesity is one of the biggest public health problems today because it affects a large part of the world's population and increase the risk of developing other diseases such as diabetes, cardiovascular disease and various types of cancer, among others. Various metabolic changes such as adipose tissue unhealthy expansion and remodeling, systemic inflammation, insulin resistance and increased free fatty acids (FFAs) in the blood can impair the functioning of several physiological systems, including the central nervous system (CNS). Previous studies have reported that obesity can alter the brain's morphology and impair learning, memory and concentration. Obesity is also considered as one of the relevants risk factors for dementia. Metabolically, the serum increase of FAs and pro-inflammatory cytokines, added to insulin resistance, can impair the glucose metabolism in the brain and stimulate the use of fatty acids as an alternative energy substrate. This can increase the production of reactive oxygen species and contribute to nerve cell damage. Previous studies of our group showed that similar metabolic changes were observed in the brain of iron-deficient animals. Coincidentally, iron deficiency (ID) is a condition more prevalent in obesity and is capable of inducing metabolic syndrome, including the accumulation of visceral fat. Furthermore, ID alters the GLUT1 's levels and glucose uptake across the blood-brain barrier (BBB). Although, how ID influences the transport of FAs has not yet been elucidated. So, the present study aims to study the transport of saturated and polyunsaturated FAs using the BBB model generated from human iPSC, in the presence of iron chelator to mimic ID. The proper functioning of the CNS is directly related to the energy metabolism in tissue. Thus, the present study may help to elucidate the mechanisms related to the energy substrates uptake/delivery in the CNS in a condition that recapitulates the metabolic alterations that occur in obesity: the FAs excess and ID, concurrently. Furthermore, since both obesity and ID can impair cognitive function, our project can make an important contribution for validating a BBB model to mimic changes that precedes sporadic neurodegenerative dementias.