NDLI: The activation of hepatic and muscle polyamine catabolism improves glucose homeostasis

Content Provider	Springer Nature Link
Author	Koponen, Taina Cerrada Gimenez, Marc Pirinen, Eija Hohtola, Esa Paananen, Jussi Vuohelainen, Susanna Tusa, Maija Pirnes Karhu, Sini Heikkinen, Sami Virkamäki, Antti Uimari, Anne Alhonen, Leena Laakso, Markku
Copyright Year	2011
Abstract	The mitochondrial biogenesis and energy expenditure regulator, PGC-1α, has been previously reported to be induced in the white adipose tissue (WAT) and liver of mice overexpressing spermidine/spermine N 1-acetyltransferase (SSAT). The activation of PGC-1α in these mouse lines leads to increased number of mitochondria, improved glucose homeostasis, reduced WAT mass and elevated basal metabolic rate. The constant activation of polyamine catabolism produces a futile cycle that greatly reduces the ATP pools and induces 5′-AMP-activated protein kinase (AMPK), which in turn activates PGC-1α in WAT. In this study, we have investigated the effects of activated polyamine catabolism on the glucose and energy metabolisms when targeted to specific tissues. For that we used a mouse line overexpressing SSAT under the endogenous SSAT promoter, an inducible SSAT overexpressing mouse model using the metallothionein I promoter (MT-SSAT), and a mouse model with WAT-specific SSAT overexpression (aP2-SSAT). The results demonstrated that WAT-specific SSAT overexpression was sufficient to increase the number of mitochondria, reduce WAT mass and protect the mice from high-fat diet-induced obesity. However, the improvement in the glucose homeostasis is achieved only when polyamine catabolism is enhanced at the same time in the liver and skeletal muscle. Our results suggest that the tissue-specific targeting of activated polyamine catabolism may reveal new possibilities for the development of drugs boosting mitochondrial metabolism and eventually for treatment of obesity and type 2 diabetes.
Starting Page	427
Ending Page	440
Page Count	14
File Format	PDF
ISSN	09394451
Journal	Amino Acids
Volume Number	42
Issue Number	2-3
e-ISSN	14382199
Language	English
Publisher	Springer Vienna
Publisher Date	2011-08-04
Publisher Place	Vienna
Access Restriction	Subscribed
Subject Keyword	Polyamine catabolism Transgenic mouse White adipose tissue Energy metabolism AMPK PGC-1α Mitochondria Neurobiology Life Sciences Biochemistry Proteomics Biochemical Engineering Analytical Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry Clinical Biochemistry

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