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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Inflammation; v. N/A, p. 15-pg., 2022-04-11.

Resumo

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)

• Processo FAPESP: 13/21026-8 - S-nitrosilação de histonas: nova via de regulação epigenética na sepse
• Beneficiário: Ricardo Costa Petroni
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/04138-2 - Sepse e tolerância ao Lipopolissacarídeo - papel da tolerância regulando o estresse oxidativo e suas consequências sobre a função mitocondrial, nitrosilação protéica e alterações do DNA
• Beneficiário: Francisco Garcia Soriano
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/13040-5 - Influência da obesidade sobre a inflamação e remodelamento pulmonar na sepse
• Beneficiário: Thais Pineda Fungaro
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica