EVALUATION OF THE CONTRIBUTION OF MITOCHONDRIA-ASSOCIATED MEMBRANES (MAMs) IN THE DEVELOPMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) DURING UNDERNUTRITION: THERAPEUTIC POTENTIAL OF TUDCA

• Grant number: 23/02152-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2023
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Everardo Magalhães Carneiro
• Grantee: Thiago dos Reis Araujo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 18/26080-4 - Characterization of molecular and functional mechanisms involved in endocrine-metabolic, cardiovascular and neural dysfunctions induced by the restriction of amino acids in vitro and in vivo: possible therapeutic role of bile acid TUDCA, AP.TEM

Abstract

Undernutrition is still a recurrent nutritional problem in low-income or middle-income countries, affecting approximately 151 million children and being responsible for 45% of deaths in children under 5 years of age worldwide. It is known that metabolic-adaptive responses resulting from protein undernutrition contribute to the development of non-communicable chronic diseases, such as non-alcoholic fatty liver disease (NAFLD). However, the molecular mechanisms responsible for the emergence of NAFLD in undernutrition remain poorly understood. Experimental evidence has suggested that disruption of the integrity of mitochondrial-associated membranes (MAMs) plays a crucial role in regulating hepatic lipid metabolism and in initiating the progression of NAFLD during obesity. Thus, we believe that disruption of the integrity of this microdomain may also play an essential role in the dysfunction of hepatic metabolism characterized by undernutrition. Furthermore, treatment with tauroursodeoxycholic acid (TUDCA) has already been shown to be effective in reversing NAFLD in different experimental models, however, it is not known whether these effects correlate with the modulation of MAMs. This work will aim for the molecular and functional characterization of the contribution of MAMs in the onset and progression of NAFLD in protein malnutrition in vivo and in vitro model. Afterward, to evaluate whether treatment with TUDCA can reverse NAFLD in undernutrition, via modulation of MAMs.