Pro-inflammatory cytokines expression and their correlation to nutrient transporters and intestinal permeability in murine treated with fatty acids

• Grant number: 20/12201-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2021
• Effective date (End): March 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Francemilson Goulart da Silva
• Grantee: Paulo Henrique Evangelista Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 22/14545-8 - Determining how high-fat diet derived fatty acids and the gut microbiota interact to engage innate immunity via pattern recognition receptors, BE.EP.DR

Abstract

The prolonged consumption of a High-Fat Diet (HFD) is associated with the development of several diseases, such as Diabetes, Cancer, cardiovascular diseases, among others. In this scenario of HFD feeding and metabolic changes, we observed a reduction of gut nutrients transporters for carbohydrates (GLUT2), peptides (PEPT1) and lipids (FAT/CD36 and NPC1L1) in mice. The most abundant fatty acids at a HFD are Palmitic Acid (PA), stearic acid (EA) and Oleic Acid (OA), which also exert regulatory actions in the inflammatory response. It is known that some chemical mediators of inflammation, such as TNF-a, may interfere with the expression of some nutrient transporters (SGLT1) and intestinal permeability, which lead us to imply that, in a condition of HFD consumption, an increase of cytokines may occur, affecting negatively the nutrient transporters expression and tight-junctions proteins in the intestine and the high levels of PA, EA and OA from HFD could stimulate it. Thus, we propose evaluating whether fatty acids administration, combined or not, in C57BL/6 mice reproduces the effects of a HFD on nutrient transporter (GLUT2, PEPT1, FAT/CD36, and NPC1L1) and tight-junctions (occludin and ZO-2) reduction as well as activating of inflammatory response. Regarding to the latter, we propose evaluating the expression of cytokines (TNF-a, IL-6, IL-1 ², IFN-g), and the JNK (total and phosphorylated levels) and nuclear NF-kB content in animals TLR4-KO. The results will allow us to correlate the potential changes in the absorption of nutrients with the intestinal inflammatory response. (AU)