Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system
Language: 
English
Abstract: 

Ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) mitochondria increases lifespan considerably in high-fat diet-fed UCP1 Tg mice compared with wild types (WT). To clarify the underlying mechanisms, we investigated substrate metabolism as well as oxidative stress damage and antioxidant defense in SM of low-fat- and high-fat-fed mice. Tg mice showed an increased protein expression of phosphorylated AMP-activated protein kinase, markers of lipid turnover (p-ACC, FAT/CD36), and an increased SM ex vivo fatty acid oxidation. Surprisingly, UCP1 Tg mice showed elevated lipid peroxidative protein modifications with no changes in glycoxidation or direct protein oxidation. This was paralleled by an induction of catalase and superoxide dismutase activity, an increased redox signaling (MAPK signaling pathway), and increased expression of stress-protective heat shock protein 25. We conclude that increased skeletal muscle mitochondrial uncoupling in vivo does not reduce the oxidative stress status in the muscle cell. Moreover, it increases lipid metabolism and reactive lipid-derived carbonyls. This stress induction in turn increases the endogenous antioxidant defense system and redox signaling. Altogether, our data argue for an adaptive role of reactive species as essential signaling molecules for health and longevity.

Author(s): 
Keipert, S.
Ost, M.
Chadt, A.
Voigt, A.
Ayala, V.
Portero-Otin, M.
Pamplona, R.
Al-Hasani, H.
Klaus, S.
Item Type: 
Journal Article
Publication Title: 
American Journal of Physiology. Endocrinology and Metabolism
Journal Abbreviation: 
Am. J. Physiol. Endocrinol. Metab.
Publication Date: 
3/1/2013
Publication Year: 
2013
Pages: 
E495-506
Volume: 
304
Issue: 
5
ISSN: 
1522-1555
DOI: 
10.1152/ajpendo.00518.2012
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23277187

Turabian/Chicago Citation

S. Keipert, M. Ost, A. Chadt, A. Voigt, V. Ayala, M. Portero-Otin, R. Pamplona, H. Al-Hasani and S. Klaus. 3/1/2013. "Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system." American Journal of Physiology. Endocrinology and Metabolism 304: 5: E495-506. 10.1152/ajpendo.00518.2012.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1152/ajpendo.00518.2012 | issn = 1522-1555 | volume = 304 | pages = E495-506 | last = Keipert | first = S. | coauthors = Ost, M., Chadt, A., Voigt, A., Ayala, V., Portero-Otin, M., Pamplona, R., Al-Hasani, H., Klaus, S. | title = Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system | journal = American Journal of Physiology. Endocrinology and Metabolism | date = 3/1/2013 | pmid = | pmc = }} </ref>