ROLE OF EXERKINES IN HEPATIC REGULATION OF NOTCH1

• Grant number: 24/06644-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: March 01, 2025
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: José Rodrigo Pauli
• Grantee: Ana Paula Azevêdo Macêdo
• Supervisor: Utpal Pajvani
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Institution abroad: Columbia University in the City of New York, United States
• Associated to the scholarship: 20/15679-2 - Effects of resistance physical exercise on Notch1 signaling pathway, and lipogenesis and gluconeogenesis process in hepatic tissue of obese mice, BP.DR

Abstract

Fatty liver disease associated with metabolic dysfunction (MAFLD) is a disease with increasing global prevalence and requires urgent strategies. It is known that activation of the Notch pathway in hepatocytes is associated with MAFLD. Activation of the Notch1 protein in hepatocytes increases triglyceride synthesis intracellularly, stabilizing the mechanistic target of rapamycin complex 1 protein (mTorc1), resulting in the upregulation of sterol regulatory element-binding protein 1c (Srebp1c) and the synthesis of hepatocyte triglycerides. Previous results in our laboratory show that physical exercise can reduce Notch1 in the liver of obese mice, but the mechanisms by which this regulation occurs are still unclear. Exercise promotes the excretion of different molecules that regulate metabolic pathways and inter tissue crosstalk, called exerkines. Therefore, to understand how exercise acts on the Notch1 pathway, it is necessary to investigate muscle-liver crosstalk. Therefore, we seek to evaluate through RNA-seq and the secretome of C2C12 cells stimulated with AICAR and HepG2 cells treated with C2C12 serum (stimulated with AICAR) to determine the myokines and hepatokines possibly involved in this Notch1 regulation process.