Short-term Obesity Worsens Heart Inflammation and Disrupts Mitochondrial Biogenesis and Function in an Experimental Model of Endotoxemia

Author(s)

Petroni, Ricardo Costa ; Souza de Oliveira, Suelen Jeronymo ; Fungaro, Thais Pineda ; Ariga, Suely K. K. ; Barbeiro, Hermes Vieira ; Soriano, Francisco Garcia ; de Lima, Thais Martins

• Document type: Journal article
• Source: Inflammation; v. N/A, p. 15-pg., 2022-04-11.

Abstract

Cardiomyopathy is a well-known complication of sepsis that may deteriorate when accompanied by obesity. To test this hypothesis we fed C57black/6 male mice for 6 week with a high fat diet (60% energy) and submitted them to endotoxemic shock using E. coli LPS (10 mg/kg). Inflammatory markers (cytokines and adhesion molecules) were determined in plasma and heart tissue, as well as heart mitochondrial biogenesis and function. Obesity markedly shortened the survival rate of mouse after LPS injection and induced a persistent systemic inflammation since TNF alpha, IL-1 beta, IL-6 and resistin plasma levels were higher 24 h after LPS injection. Heart tissue inflammation was significantly higher in obese mice, as detected by elevated mRNA expression of pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF alpha). Obese animals presented reduced maximum respiratory rate after LPS injection, however fatty acid oxidation increased in both groups. LPS decreased mitochondrial DNA content and mitochondria biogenesis factors, such as PGCla and PGC1 beta, in both groups, while NRF1 expression was significantly stimulated in obese mice hearts. Mitochondrial fusion/fission balance was only altered by obesity, with no influence of endotoxemia. Obesity accelerated endotoxemia death rate due to higher systemic inflammation and decreased heart mitochondrial respiratory capacity. (AU)

• FAPESP's process: 13/21026-8 - Histone s-nitrosylation: new pathways in epigenetic regulation during sepsis
• Grantee: Ricardo Costa Petroni
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/04138-2 - Sepsis and LPS tolerance - LPS tolerance role on oxidative stress and mithocondrial function, proteic nytrosilation and DNA damage
• Grantee: Francisco Garcia Soriano
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/13040-5 - Effect of obesity in lung inflammation and remodeling in sepsis
• Grantee: Thais Pineda Fungaro
• Support Opportunities: Scholarships in Brazil - Scientific Initiation