Cargando…
Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles
Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney pat...
Autores principales: | , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690401/ https://www.ncbi.nlm.nih.gov/pubmed/19521513 http://dx.doi.org/10.1371/journal.pone.0005894 |
_version_ | 1782167831678287872 |
---|---|
author | Hojman, Pernille Brolin, Camilla Gissel, Hanne Brandt, Claus Zerahn, Bo Pedersen, Bente Klarlund Gehl, Julie |
author_facet | Hojman, Pernille Brolin, Camilla Gissel, Hanne Brandt, Claus Zerahn, Bo Pedersen, Bente Klarlund Gehl, Julie |
author_sort | Hojman, Pernille |
collection | PubMed |
description | Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo. At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01) in EPO transfected obese mice; thus the mice weighed 21.9±0.8 g (control, normal diet,) 21.9±1.4 g (EPO, normal diet), 35.3±3.3 g (control, high-fat diet) and 28.8±2.6 g (EPO, high-fat diet). Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass. The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles. In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles. |
format | Text |
id | pubmed-2690401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26904012009-06-12 Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles Hojman, Pernille Brolin, Camilla Gissel, Hanne Brandt, Claus Zerahn, Bo Pedersen, Bente Klarlund Gehl, Julie PLoS One Research Article Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo. At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01) in EPO transfected obese mice; thus the mice weighed 21.9±0.8 g (control, normal diet,) 21.9±1.4 g (EPO, normal diet), 35.3±3.3 g (control, high-fat diet) and 28.8±2.6 g (EPO, high-fat diet). Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass. The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles. In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles. Public Library of Science 2009-06-12 /pmc/articles/PMC2690401/ /pubmed/19521513 http://dx.doi.org/10.1371/journal.pone.0005894 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Hojman, Pernille Brolin, Camilla Gissel, Hanne Brandt, Claus Zerahn, Bo Pedersen, Bente Klarlund Gehl, Julie Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles |
title | Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles |
title_full | Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles |
title_fullStr | Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles |
title_full_unstemmed | Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles |
title_short | Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles |
title_sort | erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690401/ https://www.ncbi.nlm.nih.gov/pubmed/19521513 http://dx.doi.org/10.1371/journal.pone.0005894 |
work_keys_str_mv | AT hojmanpernille erythropoietinoverexpressionprotectsagainstdietinducedobesityinmicethroughincreasedfatoxidationinmuscles AT brolincamilla erythropoietinoverexpressionprotectsagainstdietinducedobesityinmicethroughincreasedfatoxidationinmuscles AT gisselhanne erythropoietinoverexpressionprotectsagainstdietinducedobesityinmicethroughincreasedfatoxidationinmuscles AT brandtclaus erythropoietinoverexpressionprotectsagainstdietinducedobesityinmicethroughincreasedfatoxidationinmuscles AT zerahnbo erythropoietinoverexpressionprotectsagainstdietinducedobesityinmicethroughincreasedfatoxidationinmuscles AT pedersenbenteklarlund erythropoietinoverexpressionprotectsagainstdietinducedobesityinmicethroughincreasedfatoxidationinmuscles AT gehljulie erythropoietinoverexpressionprotectsagainstdietinducedobesityinmicethroughincreasedfatoxidationinmuscles |