Evaluation of miR-122 in VLDL particles and other extracellular vesicle fractions and its potential effect on adiposity in obese patients with changes in hepatic metabolism

• Grant number: 21/01860-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2023
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Adriana Souza Torsoni
• Grantee: Carolina Panzarin
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

MicroRNAs (miRNAs) are small molecules of non-coding RNAs whose primary function is the modulation of gene expression through the interaction with target messenger RNA (s). MiRNAs can be released into extracellular fluids and transported in different ways, namely I) internalized in extracellular vesicles, such as exosomes and microvesicles; II) vesicles free miRNA, bound to the Ago2 protein; III) associated with high-density lipoproteins (HDL) or IV) associated with very-low-density lipoproteins (VLDL), as recently observed. MiR-122 has broad functions in liver tissue, and more recently, its importance in regulating lipid metabolism and its role in liver inflammation has been described. In a scenario of metabolic syndrome, it is observed that miR-122 is decreased in the liver, favoring the accumulation of ectopic fat, which can trigger the onset and progression of Non-Alcoholic Fatty Liver Disease (NAFLD) through positive modulation of the synthesis triglycerides. An elevated level of miR-122 in the circulation has been strongly associated with the risk of Obesity, insulin resistance, and NAFLD; it is a possible biomarker for metabolic changes in the liver. Recent studies demonstrate the participation of miR-122 in the communication between hepatic and adipose tissue. However, little is known about this miRNA in the circulating form and whether different transport forms would define different destinations for miR-122. Knowing that VLDL can transport miRNAs to extrahepatic tissues, and considering that this lipoprotein relates to the transport of triglycerides synthesized in the liver to adipose tissue, we hypothesized that miR-122 mediates communication between the liver and tissue adipose through its carrier, especially in VLDL particles, modulating adipogenesis in obese patients with NAFLD. Therefore, the expression of miR-122 will be determined in liver, adipose tissue, and in the different fractions of serum EVs in obese patients with NAFLD. The potential effect of circulating miR-122 fractions on adipose tissue remodeling will be evaluated through in vitro tests. Thus, it is intended to characterize how circulating miR-122 acts on adipose tissue, with the perspective of identifying new mechanisms associated with the development of Obesity and associated diseases. (AU)