Aerobic exercise improves LPS-induced sepsis via regulating the Warburg effect in mice

Abstract

We investigated the impact of aerobic exercise (AE) on multiple organ dysfunction syndrome (MODS), aortic injury, pathoglycemia, and death during sepsis. ICR mice were randomized into four groups: Control (Con), Lipopolysaccharide (LPS), Exercise (Ex), and Exercise + LPS (Ex + LPS) groups. Mice were trained with low-intensity for 4 weeks. LPS and Ex + LPS mice received 5 mg/kg LPS intraperitoneally for induction of sepsis. Histopathological micrographs showed the organ morphology and damage. This study examined the effects of AE on LPS-induced changes in systemic inflammation, pulmonary inflammation, lung permeability, and bronchoalveolar lavage fluid (BALF) cell count, oxidative stress-related indicators in the lung, blood glucose levels, plasma lactate levels, serum insulin levels, plasma high-mobility group box 1 (HMGB1) levels, glucose transporter 1 (Glut1) and HMGB1, silent information regulator 1 (Sirt-1), and nuclear factor erythroid 2-related factor 2 (Nrf-2) mRNA expression levels in lung tissue. AE improved sepsis-associated multiple organ dysfunction syndrome (MODS), aortic injury, hypoglycemia, and death. AE prominently decreased pulmonary inflammation, pulmonary edema, and modulated redox balance during sepsis. AE prominently decreased neutrophil content in organ. AE prominently downregulated CXCL-1, CXCL-8, IL-6, TNF-α, Glu1, and HMGB1 mRNA expression but activated IL-1RN, IL-10, Sirt-1, and Nrf-2 mRNA expression in the lung during sepsis. AE decreased the serum levels of lactate and HMGB1 but increased blood glucose levels and serum insulin levels during sepsis. A 4-week AE improves sepsis-associated MODS, aortic injury, pathoglycemia, and death. AE impairs LPS-induced lactate and HMGB1 release partly because AE increases serum insulin levels and decreases the levels of Glut1. AE is a novel therapeutic strategy for sepsis targeting aerobic glycolysis.

Roles of cuproptosis-related gene DLAT in various cancers: a bioinformatic analysis and preliminary verification on pro-survival autophagy

“…Mitochondrial pyruvate dehydrogenase complex (PDC) catalyzes the irreversible decarboxylation of pyruvate, a product of glycolysis, to produce acetyl coenzyme A and enter the tricarboxylic acid cycle, thus playing a crucial role in cellular catabolic glucose pathway ( Stacpoole, 2017 ). The Warburg effect confirms that the marker of tumor metabolism is aerobic glycolysis rather than the mitochondrial oxidation of pyruvate ( Bencze et al, 2021 ; Wang, Wang & Tang, 2021 ; Wen et al, 2021 ). Studies have suggested that mitochondrial function is weakened by the inhibition of PDC, causing metabolic changes in tumor cells.…”

Single-Cell Sequencing Reveals the Regulatory Role of Maresin1 on Neutrophils during Septic Lung Injury

“…All of the Cxcl3, Ccl3, Ccl4, and Icam1 play an important role in the migration of neutrophils [ 38 , 39 , 40 , 41 ]. It is worth noting that the expression of Il1rn, as an anti-inflammatory gene [ 42 ], was up-regulated in the CLP group, which may be caused by auto-protective regulation. Maresin1 can significantly reduce the expression of the Cxcl3, Ccl3, Ccl4, and Icam1 genes in the Neutrophil3-Cxcl3 subpopulation, which may be an important mechanism by which Maresin1 regulates neutrophil function, and also provides a possible intervention target for the treatment of septic lung injury.…”

Roles and Molecular Mechanisms of Physical Exercise in Sepsis Treatment

“…Numerous studies have shown that physical exercise improves organ dysfunction by reducing systemic inflammation in sepsis patients. Wang et al (2021) found that aerobic exercise decreased lung neutrophil content and the mRNA expression levels of IL-6, TNF-α, Glu1, CXCL-1, and HMGB1 in the lung to improve respiratory dysfunction. Shimojo et al (2019) showed that swimming decreased serum inflammatory cytokines and increased anti-inflammatory cytokines by decreasing dopamine.…”

“…Here, we discuss whether physical exercise affects the outcomes of sepsis. Based on experimental models, several studies have suggested that regular exercise alters the morbidity of sepsis and increases the survival rate ( Sossdorf et al, 2013 ; Kim and Kang, 2019 ; Wang et al, 2021 ). In a clinical study, Wang et al (2014) indicated an association between physical exercise preconditioning and susceptibility to sepsis.…”