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

Nobuyasu Komazawa, Morihiro Matsuda, Gen Kondoh, Wataru Mizunoya, Masanori Iwaki, Toshiyuki Takagi, Yasuyuki Sumikawa, Kazuo Inoue, Akira Suzuki, Tak Wah Mak, Toru Nakano, Tohru Fushiki, Junji Takeda, Iichiro Shimomura

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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 proliferate 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.

Original languageEnglish
Pages (from-to)1208-1215
Number of pages8
JournalNature medicine
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 1 2004

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Komazawa, N., Matsuda, M., Kondoh, G., Mizunoya, W., Iwaki, M., Takagi, T., ... Shimomura, I. (2004). Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice. Nature medicine, 10(11), 1208-1215. https://doi.org/10.1038/nm1117