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Title:
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Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system
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Author:
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Keipert, Susanne; Ost, Mario; Chadt, A.; Voigt, A.; Ayala Jové, Ma. Victoria (Maria Victoria); Portero Otín, Manuel; Pamplona Gras, Reinald; Al-Hasani, H.; Klaus, Susanne
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Notes:
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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.
The research leading to these results has received funding from the
European Union’s Seventh Framework Program FP7 2007–2013 under grant
agreement no. 244995 (BIOCLAIMS Project) and from the German Research
Foundation (DFG: KL613/14-2). The studies conducted at the Department of
Experimental Medicine were supported in part by research and development
grants from the Spanish Ministry of Science and Innovation (BFU2009 –
11879/BFI), the Spanish Ministry of Health (PI08111532), the Autonomous
Government of Catalonia (2009SGR735), and COST B35 Action of the
European Union. |
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Subject(s):
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-Uncoupling protein 1
-AMP-activated protein kinase
-Oxidative
-Stress |
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Rights:
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(c) The American Physiological Society, 2013
info:eu-repo/semantics/restrictedAccess |
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Document type:
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article
publishedVersion |
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Published by:
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American Physiological Society
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