Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats
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 carbohydrate metabolism during lipopolysaccharide (...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Published: |
Portland Press
2017
|
| Subjects: | |
| Online Access: | https://eprints.nottingham.ac.uk/44180/ |
| _version_ | 1848796856518180864 |
|---|---|
| author | Crossland, Hannah Constantin-Teodosiu, Dumitru Gardiner, Sheila M. Greenhaff, Paul L. |
| author_facet | Crossland, Hannah Constantin-Teodosiu, Dumitru Gardiner, Sheila M. Greenhaff, Paul L. |
| author_sort | Crossland, Hannah |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 carbohydrate metabolism 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 two 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 tumor 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 upregulation 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. |
| first_indexed | 2025-11-14T19:54:38Z |
| format | Article |
| id | nottingham-44180 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:54:38Z |
| publishDate | 2017 |
| publisher | Portland Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-441802024-08-15T15:22:59Z https://eprints.nottingham.ac.uk/44180/ Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats Crossland, Hannah Constantin-Teodosiu, Dumitru Gardiner, Sheila M. Greenhaff, Paul L. 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 carbohydrate metabolism 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 two 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 tumor 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 upregulation 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. Portland Press 2017-06-23 Article PeerReviewed Crossland, Hannah, Constantin-Teodosiu, Dumitru, Gardiner, Sheila M. and Greenhaff, Paul L. (2017) Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats. Clinical Science, 131 (13). pp. 1437-1447. ISSN 1470-8736 sepsis inflammation muscle atrophy muscle insulin resistance http://www.clinsci.org/content/131/13/1437 doi:10.1042/CS20170958 doi:10.1042/CS20170958 |
| spellingShingle | sepsis inflammation muscle atrophy muscle insulin resistance Crossland, Hannah Constantin-Teodosiu, Dumitru Gardiner, Sheila M. Greenhaff, Paul L. Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats |
| title | Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats |
| title_full | Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats |
| title_fullStr | Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats |
| title_full_unstemmed | Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats |
| title_short | Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats |
| title_sort | peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats |
| topic | sepsis inflammation muscle atrophy muscle insulin resistance |
| url | https://eprints.nottingham.ac.uk/44180/ https://eprints.nottingham.ac.uk/44180/ https://eprints.nottingham.ac.uk/44180/ |