Effect of modified citrus pectin on hepatic autophagy in metabolic dysfunction-associated steatohepatitis

• Grant number: 24/20313-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: João Paulo Gabriel Camporez
• Grantee: Helena Gaspar Monteiro
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Sedentary lifestyle and increased consumption of a high-fat diet largely contribute to the development of cardiometabolic risks, such as obesity, insulin resistance, type 2 diabetes (T2DM) and cardiovascular diseases. Several mechanisms are currently considered to cause insulin resistance, such as abnormal metabolism and ectopic lipid accumulation, mitochondrial dysfunction, as well as inflammation and endoplasmic reticulum stress. Furthermore, another complication associated with metabolic diseases is Fatty Liver Disease Associated with Metabolic Dysfunction (MAFLD). Furthermore, MAFLD can progress to a more severe stage, presenting characteristics such as macro and/or microvesicular steatosis, mixed lobular inflammatory infiltrate and hepatocellular ballooning in the centrilobular vein area (zone III), and may present fibrosis and Mallory bodies, being known this clinical condition as Steatohepatitis Associated with Metabolic Dysfunction (MASH). Another factor that has been demonstrated to impact metabolism is autophagy, which is a process of recycling cytoplasmic cellular content, conserved throughout evolution and present in several systems, with the main function of maintaining homeostasis, through the degradation of components. cells - such as proteins, lipids, organelles, glycogen, among others - which promotes the conservation of the "quality" of cellular content. Specifically in the liver, dysregulation of the autophagic process leads to the accumulation of hepatic triglycerides and the development of steatosis, which is generally associated with insulin resistance. Furthermore, with the increasing prevalence of MASH, this pathology has become one of the main etiological factors of hepatocellular cancer (HCC) and liver transplantation. Still, there is no specific treatment indicated for MASH. Therefore, the general objective of this project is to study the effects of Modified Citrus Pectin (MCP), which is considered a functional food and has the effect of inhibiting Galectin-3 (Gal-3), on hepatic autophagy in an experimental model of MASH.