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.

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.

Department of Social and Environmental Medicine, Graduate School of Frontier Bioscience, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Osaka

Department of Medicine and Pathophysiology, Graduate School of Frontier Bioscience, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Osaka

Morihiro Matsuda, Masanori Iwaki, Toshiyuki Takagi & Iichiro Shimomura

Division of Food Science and Biotechnology, Laboratory of Nutrition Chemistry, Graduate School of Agriculture, Kyoto University, Kitashirakawa, Sakyo-ku, 606-8502, Kyoto

Department of Dermatology, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Osaka

Department of Biochemistry, Akita University, 1-1 Hondou, Akita, 010-8543, Akita, Japan

Advanced Medical Discovery Institute, University of Toronto, Toronto, M5G 2Cl, Ontario, Canada

Department of Pathology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Osaka

Center for Advanced Science and Innovation, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Osaka

Department of Internal Medicine and Molecular Science, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Osaka

PREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, 332-0012, Saitama, Japan

Expression analyses of Cre in Adiponectin promoter-driven Cre transgenic mice. (PDF 34 kb)

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