Low-intensity exercise in the acute phase of lipopolysaccharide-induced sepsis improves lipid metabolism and survival in mice by stimulating PGC-1α expression.

Abstract

The effect of exercise during the acute phase following sepsis onset is poorly understood. We investigated how low-intensity exercise during acute sepsis alters energy-substrate metabolism and survival in mice with lipopolysaccharide (LPS)-induced sepsis. Mice were divided into control (C, saline), low-dose LPS (L, 1 mg/kg), medium-dose LPS (M, 5 mg/kg), and high-dose LPS (H, 10 mg/kg) groups. Each group was subdivided into sedentary (SED) and exercise (EX) groups; the EX group mice were exercised at low intensity on a treadmill after LPS administration. Survival proportions and vital functions were measured, and indirect calorimetry through respiratory gas analysis was performed until 72 hours after treatment. Organ weight and lipid levels in the plasma and liver were measured, and the messenger RNA and protein levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) were evaluated using quantitative polymerase chain reaction and Western blotting. Survival proportions of H-EX mice were higher than those of H-SED mice. At 16 hours after LPS administration, fatty acid oxidation was decreased in M-SED and H-SED groups but increased in all EX groups and was higher in surviving mice in H-SED and H-EX groups than in nonsurviving mice, suggesting that fatty acid oxidation is related to survival. Epididymal fat weight was lower in the EX groups than in the SED groups, whereas plasma and liver lipid levels were elevated in all EX groups; this suggests that exercise induces the transport of lipids from endogenous fat into the blood and the liver for use as the energy source. Lastly, PGC-1α messenger RNA and protein levels were lower in L-, M-, and H-SED groups than in the C-SED group but were high in all EX groups. Our study provides the revolutionary finding that exercise during the acute phase following sepsis onset might exert a therapeutic effect.