The impact of nutrient intervention on the mitochondrial fragmentation process in POMC neurons

• Grant number: 24/14933-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2025
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Licio Augusto Velloso
• Grantee: Julia Moreira da Silva
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Hypothalamic pro-opiomelanocortin neurons act as first-order sensors of systemic signals that reflect the body's energy reserves. In diet-induced obesity, pro-opiomelanocortin neurons are structurally and functionally damaged, resulting in defective regulation of energy balance. It has previously been shown that inducing mild stress in these neurons can protect them from damage caused by the consumption of a high-fat diet, mitigating the development of obesity. However, the cellular mechanisms behind mitochondrial changes in pro-opiomelanocortin neurons are currently unknown. In this project, we will subject a cell line of pro- opiomelanocortin neurons to nutritional interventions, such as; elevated or reduced levels of glucose, elevated levels of palmitate, and elevated levels of aspartate, in the process of functional and structural remodeling of mitochondria. To this end, pro-opiomelanocortin neurons cultured under control conditions will be compared to neurons exposed to each of the above conditions, for a short period (6h) or long period (48h) and will then be used in experiments in which important markers will be measured. the structure and function of mitochondria, such as the production of reactive oxygen species, measurement of mitochondrial respiration and ATP production; determination of mitochondrial sphericity, mitochondrial branching, and expression of transcripts that encode proteins involved in the mitochondrial fusion/fission cycle. We believe that this project could contribute to advances in the understanding of disorders of pro-opiomelanocortin neurons in situations of damage caused by excess nutrients, as occurs in obesity. (AU)