Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice.
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.
Komazawa
Nobuyasu
N
Department of Social and Environmental Medicine, Graduate School of Frontier Bioscience, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan.
Matsuda
Morihiro
M
Kondoh
Gen
G
Mizunoya
Wataru
W
Iwaki
Masanori
M
Takagi
Toshiyuki
T
Sumikawa
Yasuyuki
Y
Inoue
Kazuo
K
Suzuki
Akira
A
Mak
Tak Wah
TW
Nakano
Toru
T
Fushiki
Tohru
T
Takeda
Junji
J
Shimomura
Iichiro
I
D052242:Adiponectin; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers; D004734:Energy Metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009765:Obesity / Q000517:prevention & control*; D051059:PTEN Phosphohydrolase; D010716:Phosphatidylinositols / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D022722:Thermogenesis / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D052242:Adiponectin; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D010716:Phosphatidylinositols; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human