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

BACKGROUND: 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. METHODS: 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 h after treatment. Organ weight and lipid levels in the plasma and liver were measured, and the mRNA and protein levels of peroxisome proliferator-activated receptor-[gamma] coactivator-1[alpha] (PGC-1[alpha]) were evaluated using quantitative polymerase chain reaction and western blotting. RESULTS: Survival proportions of H-EX mice were higher than those of H-SED mice. At 16 h after LPS administration, fatty acid oxidation (FAO) was decreased in M- 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 non-surviving mice, suggesting that FAO is related to survival. Epididymal fat weight was lower in EX groups than in 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 blood and the liver for use as the energy source. Lastly, PGC-1[alpha] mRNA and protein levels were lower in L-, M-, and H-SED groups than in C-SED group, but were high in all EX groups. CONCLUSION: Our study provides the revolutionary finding that exercise during the acute phase following sepsis onset might exert a therapeutic effect. (C) 2016 Lippincott Williams & Wilkins, Inc.

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