Sepsis Impairs Thyroid Hormone Signaling and Mitochondrial Function in the Mouse Diaphragm

Bloise, Flávia Fonseca; Santos, Anderson Teixeira; Brito, Juliana; Andrade, Cherley Borba Vieira de; Oliveira, Thamires Siqueira; Souza, Aline F. P.; Fontes, Klaus N.; Silva, Johnatas D.; Blánco, N.; Silva, Pedro L.; Rocco, Patrícia Rieken Macêdo; Fliers, Eric; Boelen, Anita; da‐Silva, Wagner Seixas; Ortiga-Carvalho, Tânia Maria

doi:10.1089/thy.2019.0124

Cited by 19 publications

(20 citation statements)

References 35 publications

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“…Thus, it could be an adaptation process to handle septic mitochondrial damage. We previously demonstrated that acute sepsis (24 h CLP) decreases the critical cellular antioxidative protein expression in septic diaphragms ( Bloise et al, 2020 ). Therefore, the disruption in mitochondrial physiology induced by CLP demonstrated here could be one factor that leads to diaphragm dysfunction during sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…We have demonstrated previously that 24 h after CLP, the mitochondrial function is already decreased. However, the diaphragm sarcomeric organization is preserved ( Bloise et al, 2020 ). Herein, the diaphragm function did not change; however, the sarcomeric organization seems impaired ( Figure 2B ).…”

Section: Discussionmentioning

confidence: 99%

“…CLP is the gold standard murine sepsis model ( Laudanski, 2021 ). Sepsis was induced in the experimental group by CLP; control animals were sham-operated as described previously ( Rittirsch et al, 2009 ; Bloise et al, 2020 ). In brief, after anesthetized with ketamine (100 mg/kg; Cristália, Itapira, Brazil) and xylazine (10 mg/kg; Syntec, Barueri, Brazil) intraperitoneally, the cecum was located, and below the ileocecal valve the cecal ligation was performed.…”

Section: Methodsmentioning

confidence: 99%

“…Transmission electron microscopy (TEM) and mitochondrial quantification were performed as described previously ( Bloise et al, 2020 ). In brief, diaphragms were immersed in 4% of paraformaldehyde for at least 48 h. The samples were then processed and analyzed (qualitatively and quantitatively) using a JEM1011 microscope (JEOL, Akishima, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…Diaphragm weakness can be correlated with the mortality rate in intensive care units ( Supinski et al, 2018 ). Our group recently demonstrated that severe untreated acute sepsis could reduce the mitochondrial number in the diaphragm and show unbalance in thyroid hormone signaling related to mitochondrial impairment in the diaphragm ( Bloise et al, 2020 ). The mechanisms associated with diaphragm dysfunction during treated and more prolonged sepsis are still not well understood.…”

Section: Introductionmentioning

confidence: 99%

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Sepsis Disrupts Mitochondrial Function and Diaphragm Morphology

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sepsis Disrupts Mitochondrial Function and Diaphragm Morphology

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Metabolic reprogramming consequences of sepsis: adaptations and contradictions

Liu

Zhou

Wang

et al. 2022

Cell. Mol. Life Sci.

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During sepsis, the importance of alterations in cell metabolism is underappreciated. The cellular metabolism, which has a variable metabolic profile in different cells and disease stages, is largely responsible for the immune imbalance and organ failure associated with sepsis. Metabolic reprogramming, in which glycolysis replaces OXPHOS as the main energy-producing pathway, is both a requirement for immune cell activation and a cause of immunosuppression. Meanwhile, the metabolites produced by OXPHOS and glycolysis can act as signaling molecules to control the immune response during sepsis. Sepsisinduced "energy shortage" leads to stagnated cell function and even organ dysfunction. Metabolic reprogramming can alleviate the energy crisis to some extent, enhance host tolerance to maintain cell survival functions, and ultimately increase the adaptation of cells during sepsis. However, a switch from glycolysis to OXPHOS is essential for restoring cell function. This review summarized the crosstalk between metabolic reprogramming and immune cell activity as well as organ function during sepsis, discussed the benefits and drawbacks of metabolic reprogramming to show the contradictions of metabolic reprogramming during sepsis, and assessed the feasibility of treating sepsis through targeted metabolism. Using metabolic reprogramming to achieve metabolic homeostasis could be a viable therapy option for sepsis.

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Protective effects of farnesyltransferase inhibitor on sepsis-induced morphological aberrations of mitochondria in muscle and increased circulating mitochondrial DNA levels in mice

Tsuji

Nakazawa

Yorozu

et al. 2021

Biochemical and Biophysical Research Communications

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Sepsis remains a leading cause of mortality in critically ill patients and is characterized by multi-organ dysfunction. Mitochondrial damage has been proposed to be involved in the pathophysiology of sepsis. In addition to metabolic impairments resulting from mitochondrial dysfunction, mitochondrial DNA (mtDNA) causes systemic inflammation as a damage-associated molecular pattern when it is released to the circulation. Metabolic derangements in skeletal muscle are a major complication of sepsis and negatively affects clinical outcomes of septic patients. However, limited knowledge is available about sepsis-induced mitochondrial damage in skeletal muscle. Here, we show that sepsis induced profound abnormalities in cristae structure, rupture of the inner and outer membranes and enlargement of the mitochondria in mouse skeletal muscle in a time-dependent manner, which was associated with increased plasma mtDNA levels. Farnesyltransferase inhibitor, FTI-277, prevented sepsis-induced morphological aberrations of the mitochondria, and blocked the increased plasma mtDNA levels along with improved survival. These results indicate that protein farnesylation plays a role in sepsis-induced damage of the mitochondria in mouse skeletal muscle. Our findings suggest that mitochondrial disintegrity in skeletal muscle may contribute to elevated circulating mtDNA levels in sepsis.

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Sepsis Impairs Thyroid Hormone Signaling and Mitochondrial Function in the Mouse Diaphragm

Cited by 19 publications

References 35 publications

Sepsis Disrupts Mitochondrial Function and Diaphragm Morphology

Sepsis Disrupts Mitochondrial Function and Diaphragm Morphology

Metabolic reprogramming consequences of sepsis: adaptations and contradictions

Protective effects of farnesyltransferase inhibitor on sepsis-induced morphological aberrations of mitochondria in muscle and increased circulating mitochondrial DNA levels in mice

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