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 language | English |
|---|---|
| Pages (from-to) | 1208-1215 |
| Number of pages | 8 |
| Journal | Nature medicine |
| Volume | 10 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2004 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice. / Komazawa, Nobuyasu; Matsuda, Morihiro; Kondoh, Gen; Mizunoya, Wataru; Iwaki, Masanori; Takagi, Toshiyuki; Sumikawa, Yasuyuki; Inoue, Kazuo; Suzuki, Akira; Mak, Tak Wah; Nakano, Toru; Fushiki, Tohru; Takeda, Junji; Shimomura, Iichiro.
In: Nature medicine, Vol. 10, No. 11, 01.11.2004, p. 1208-1215.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice
AU - Komazawa, Nobuyasu
AU - Matsuda, Morihiro
AU - Kondoh, Gen
AU - Mizunoya, Wataru
AU - Iwaki, Masanori
AU - Takagi, Toshiyuki
AU - Sumikawa, Yasuyuki
AU - Inoue, Kazuo
AU - Suzuki, Akira
AU - Mak, Tak Wah
AU - Nakano, Toru
AU - Fushiki, Tohru
AU - Takeda, Junji
AU - Shimomura, Iichiro
PY - 2004/11/1
Y1 - 2004/11/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nm1117
DO - 10.1038/nm1117
M3 - Article
VL - 10
SP - 1208
EP - 1215
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 11
ER -