Brown adipose tissue thermogenesis role on the mild therapeutic hypothermia in premature patients with necrotizing enterocolitis: NEOTHERM project

• Grant number: 21/01107-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2022
• End date: July 31, 2025
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Walusa Assad Gonçalves Ferri
• Grantee: Walusa Assad Gonçalves Ferri
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Cristina Helena Faleiros Ferreira ; José Carlos Farias Alves Filho ; Lourenço Sbragia Neto ; Luiz Osório Silveira Leiria

Abstract

Prematurity is a significant cause of infant mortality in Brazil. Furthermore, necrotizing enterocolitis (NEC) is one of the leading causes of morbidity and mortality in this age group. NEC etiology is not understood. However, the disease is associated with a breakdown of the gastrointestinal epithelium barrier associated with developing an exacerbated inflammatory response and consequent tissue damage, similar to the ischemia-reperfusion process. It evolves into severe forms of the disease that commonly leads to multiple organ failure. Despite extensive research efforts over the past few decades, the proposed treatments are still limited and ineffective. Hypothermia is a therapeutic proposal for several diseases, has been used successfully in hypoxic-ischemic encephalopathy in the asphyxiated newborn. More recently, this therapy has been proposed to NEC treatment with promising results, demonstrating a protective effect of hypothermia on inflammatory aspects and increasing patients' survival rate. Despite promising clinical results, the mechanisms by which therapeutic hypothermia decreases the exacerbated inflammatory response in the severe form of the disease are still unclear, and this knowledge could be useful in treating other neonatal diseases. One aspect of being considered is the role of brown adipose tissue in neonatal diseases. The brown adipose tissue has been the target of several recent research, which showed its endocrine function with an essential role in energy regulation and its role as a secretory organ of inflammatory mediators that act in the immunomodulation of the inflammatory response. In the full-term newborn, the brown adipose tissue is well-developed and is responsible for the term regulation-however, in premature newborns, few brown tissues quantitative ant the adipose function tissue. Evidence in the literature indicates that the increase in thermogenic activity of brown adipose tissue, induced by hypothermia, leads to the production and secretion of lipid mediators with anti-inflammatory and pro-resolving activity. The applicability of this action in neonatal diseases may represent innovation and evolution in treating various diseases, mainly NEC. Therefore, this project assesses the hypothermia repercussions on brown fat's anti-inflammatory activity and the association with the outcome. (AU)