Galectin-3 as a Potential Therapeutic Target for Non-Alcoholic Steatohepatitis and Hepatic Insulin Resistance

• Grant number: 24/03604-9
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: João Paulo Gabriel Camporez
• Grantee: João Paulo Gabriel Camporez
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Lifestyle and increased calorie consumption largely contribute to the development of obesity, insulin resistance, type 2 diabetes (T2DM) and cardiovascular disease. This excessive consumption of high-calorie foods, with inadequate satiety and very palatable, has promoted an increase in obesity and, as a consequence, an increase in the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD), which reaches around 30% of adults and 10% of children in developed countries. NAFLD has a wide spectrum of histological abnormalities, which can evolve into Non-Alcoholic Steatohepatitis (NASH), characterized by macro and/or microvesicular steatosis, inflammatory infiltrate and hepatocellular ballooning in the area of the centrilobular vein (zone III), which may present fibrosis and corpuscles of Mallory. As the liver is a central organ in the control of energy metabolism, impairment of its functioning plays an important role in the development of insulin resistance and DM2. A protein known as Galectin-3 (Gal-3) is elevated in the plasma of both obese humans and rodents, with studies suggesting that this protein contributes to obesity-related insulin resistance and inflammation. Furthermore, we demonstrated in a study by our group that Gal-3 expression is increased in the liver of an experimental model of NASH (Camargo et al., 2022). Other studies have also shown that the absence of Gal-3 protects mice against kidney and liver fibrosis, in addition to improving immune function. Suggesting that Gal-3 may play a role in the liver in the development or severity of NASH and hepatic insulin resistance. Therefore, the objective of this project is to study the therapeutic potential of Gal-3 inhibition in the development of NASH and hepatic insulin resistance in an experimental model. (AU)