@article{51e28496b18d45a9b90bae134c6ba217,
title = "Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice",
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.",
author = "Nobuyasu Komazawa and Morihiro Matsuda and Gen Kondoh and Wataru Mizunoya and Masanori Iwaki and Toshiyuki Takagi and Yasuyuki Sumikawa and Kazuo Inoue and Akira Suzuki and Mak, {Tak Wah} and Toru Nakano and Tohru Fushiki and Junji Takeda and Iichiro Shimomura",
note = "Funding Information: We thank Y. Matsuzawa and K. Sugihara for their encouragement, and K. Nishida, K. Oiki and S. Mizuno for technical assistance. This work was supported in part by grants from the Suzuken Memorial Foundation, The Nakajima Foundation, Kanae Foundation for Life and Socio-Medical Science, The Tokyo Biochemical Research Foundation, Takeda Medical Research Foundation, Uehara Memorial Foundation, Takeda Science Foundation, Novartis Foundation (Japan) for the Promotion of Science, The Cell Science Research Foundation, The Mochida Memorial Foundation for Medical and Pharmaceutical Research, a Grant-in-Aid from the Japan Medical Association, The Naito Foundation, a grant from the Japan Heart Foundation Research, Kato Memorial Bioscience Foundation, Japan Research Foundation for Clinical Pharmacology, a grant from the Ministry of Health, Labor and Welfare, Japan, and Grants-in-Aid from COE Research and Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology, Japan. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",
year = "2004",
month = nov,
doi = "10.1038/nm1117",
language = "English",
volume = "10",
pages = "1208--1215",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "11",
}