Abstract:
:Pten is an important phosphatase, suppressing the phosphatidylinositol-3 kinase/Akt pathway. Here, we generated adipose-specific Pten-deficient (AdipoPten-KO) mice, using newly generated Acdc promoter-driven Cre transgenic mice. AdipoPten-KO mice showed lower body and adipose tissue weights despite hyperphagia and enhanced insulin sensitivity with induced phosphorylation of Akt in adipose tissue. AdipoPten-KO mice also showed marked hyperthermia and increased energy expenditure with induced mitochondriagenesis in adipose tissue, associated with marked reduction of p53, inactivation of Rb, phosphorylation of cyclic AMP response element binding protein (CREB) and increased expression of Ppargc1a, the gene that encodes peroxisome proliferative activated receptor gamma coactivator 1 alpha. Physiologically, adipose Pten mRNA decreased with exposure to cold and increased with obesity, which were linked to the mRNA alterations of mitochondriagenesis. Our results suggest that altered expression of adipose Pten could regulate insulin sensitivity and energy expenditure. Suppression of adipose Pten may become a beneficial strategy to treat type 2 diabetes and obesity.
journal_name
Nat Medjournal_title
Nature medicineauthors
Komazawa N,Matsuda M,Kondoh G,Mizunoya W,Iwaki M,Takagi T,Sumikawa Y,Inoue K,Suzuki A,Mak TW,Nakano T,Fushiki T,Takeda J,Shimomura Idoi
10.1038/nm1117keywords:
subject
Has Abstractpub_date
2004-11-01 00:00:00pages
1208-15issue
11eissn
1078-8956issn
1546-170Xpii
nm1117journal_volume
10pub_type
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