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- Title
Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscleprotein loss and lactate accumulation in rats.
- Authors
Crossland, Hannah; Constantin-Teodosiu, Dumitru; Gardiner, Sheila M.; Greenhaff, Paul L.
- Abstract
The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydratemetabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5 ± 0.1 mg. kg-1 . day-1) for 2 weeks before and during 24 h continuous intravenous infusion of LPS (15 μg . kg-1 . h-1) or saline. Rosi blunted LPS-induced increases in muscle tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA by 70% (P<0.05) and 64% (P<0.01) respectively. Furthermore, Rosi suppressed the LPS-induced reduction in phosphorylated AKT and phosphorylated Forkhead box O (FOXO) 1 protein, as well as the up-regulation of muscle RING finger 1 (MuRF1; P<0.01) mRNA and the LPS-induced increase in 20S proteasome activity (P<0.05). Accordingly, LPS reduced the muscle protein:DNA ratio (∼30%, P<0.001), which Rosi offset. Increased muscle pyruvate dehydrogenase kinase 4 (PDK4) mRNA (P<0.001) and muscle lactate accumulation (P<0.001) during endotoxaemia were suppressed by Rosi. Thus, pre-treatment with Rosi reduced muscle cytokine accumulation and blunted muscle protein loss and lactate accumulation during endotoxaemia and at least in part by reducing activation of molecular events known to increase muscle protein breakdown and mitochondrial pyruvate use.
- Subjects
PEROXISOMES; MICROBODIES; TREATMENT of endotoxemia; ENDOTOXEMIA prevention; LACTATES; THERAPEUTICS
- Publication
Clinical Science, 2017, Vol 131, Issue 13, p1437
- ISSN
0143-5221
- Publication type
Article
- DOI
10.1042/CS20170958