The role of adipose tissue derived microRNAs in obesity- and lipodystrophy-induced non-alcoholic fatty liver disease

• Grant number: 25/00205-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2025
• End date: April 30, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Giovanna Leite dos Santos
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/08354-2 - The interplay between the immune system and metabolism as a key determinant of the aging process, AP.TEM

Abstract

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome and it affects more than 25% of the global population. Due to its complexity and still not completely elucidated underlying etiology, NAFLD remains without approved pharmacological treatment. Obesity and lipodystrophy are both associated with adipose tissue dysfunction and ectopic lipid accumulation. Moreover, adipose tissue is a major source of circulating microRNAs, which reach multiple tissues participating in inter-organ communication. The circulating microRNA pattern is altered in metabolic diseases, emphasizing their possible involvement in disease development and progression. Therefore, we hypothesize that both obesity and lipodystrophy lead to hepatic steatosis; however, we posit that an altered microRNA profile among adipose tissue secreted extracellular vesicles is required to trigger steatosis progression to non-alcoholic steatohepatitis. To address this hypothesis, we are going to use in vivo (mouse) models to investigate the role of microRNAs in NAFLD progression. Specific objectives are #1: to evaluate obesity- and lipodystrophy-induced changes in the total pool of plasma extracellular vesicle microRNA profile; #2: to investigate whether NAFLD progression to NASH is dependent on adipose tissue secreted extracellular vesicles and #3: To identify hepatic target for the altered microRNAs in plasma and validate the role of the identified microRNAs in the NAFLD pathophysiology in vivo. Considering the role of microRNAs in gene expression and metabolism, they are plausible therapeutics for NAFLD. Identifying mechanistic links involved in NAFLD is an important step towards better therapeutic and diagnostic approaches for this condition.