Investigation of the Properties of Medium-Chain N-Acylglycines in Modulating Energy Metabolism in the Context of Dietary Restriction

• Grant number: 24/01504-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2025
• End date: February 29, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Julya Raquel Simões Nascimento
• 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

The project aims to deepen the understanding of the effects of N-Heptanoylglycine (C7-Gly), a medium-chain N-acylglycine (CM-NAG), over energy metabolism. C7-Gly has been identified as decreased in the circulation of rodents subjected to dietary restriction (DR) and demonstrates the ability to stimulate the gene encoding uncoupling protein 1 (UCP1) in brown adipocytes. Within the scope of the project, this molecule will be investigated both in vitro and in vivo, seeking to elucidate the pathways of synthesis, degradation, and action of this bioactive lipid in the context of DR. In the initial phase, mice will be subjected to DR, with and without the application of C7-Gly. Subsequently, metabolic assessments will be conducted to understand the impact of dietary intervention and the application of C7-Gly. Following this, we will analyze the gene expression pattern of brown adipose tissue (BAT) in these mice. This will involve RNA sequencing (RNA-seq) of BAT from mice subjected to the various experimental conditions, as well as differentiated adipocytes incubated with the serum fraction of these animals. The generated data will be analyzed using bioinformatics, allowing the identification of altered pathways, which will be subsequently investigated in different tissues of the animals to establish a more comprehensive physiological role of C7-Gly. Moreover, there will be conducted an evaluation of gene expression of biosynthetic enzymes and ligands of C7-Gly in different tissues associated with energy metabolism, aiming to establish, with this set of analyses, the location and the behavior of the pathways related to the biological processes mediated by C7-Gly in the context of DR. The project aims to contribute to a more comprehensive understanding of CM-NAGs and a potential application of these acyl-amino acids in metabolic diseases and obesity.