Access

Article


Nature Medicine 10, 1208 - 1215 (2004)
Published online: 17 October 2004 | doi:10.1038/nm1117



There is a Retraction (June 2005) associated with this Article.

Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice

Nobuyasu Komazawa1, Morihiro Matsuda2, Gen Kondoh1, Wataru Mizunoya3, Masanori Iwaki2, Toshiyuki Takagi2, Yasuyuki Sumikawa4, Kazuo Inoue3, Akira Suzuki5, Tak Wah Mak6, Toru Nakano7, Tohru Fushiki3, Junji Takeda1,8 & Iichiro Shimomura2,9,10


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.


MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NEWS AND VIEWS

Turning up the heat in the fat cell

Nature Medicine News and Views (01 Nov 2004)

Turning WAT into BAT gets rid of fat

Nature Medicine News and Views (01 Oct 2001)

See all 3 matches for News And Views