【2004年10月18日】 　特定の酵素を脂肪組織からなくすと、たくさん食べても体重が減ることを下村伊一郎（しもむら・いいちろう）・大阪大教授（内分泌代謝学）らがマウスの実験で突き止めた。肥満による糖尿病などの生活習慣病治療につながる可能性があるという。米医学誌ネイチャー・メディシンに18日発表した。

　下村教授らはマウスが太ると脂肪組織内で増える酵素「ＰＴＥＮ」に着目。脂肪組織だけでＰＴＥＮをなくしたマウスを作成し実験した。

　このマウスは、普通のマウスと比べ食事量が約2割増えたのに、体重は２５％減った。マウスの体内では、脂肪組織のエネルギーを燃やすミトコンドリアが増え、血糖量を低下させるインスリンが効きやすくなっていた。

　肝臓などでＰＴＥＮをなくすと発がんにつながるとの報告があり、下村教授は「治療に使うには、脂肪組織だけでＰＴＥＮを抑える薬を効かせる技術が必要になる」と話している。

Nature Medicine

Published online: 17 October 2004; | doi:10.1038/nm1117

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

Nobuyasu Komazawa1, Morihiro Matsuda2, Gen Kondoh1, Wataru Mizunoya3, Masanori Iwaki2, Toshiyuki Takagi2, Yasuyuki Sumikawa4, Kazuo Inoue3, Akira Suzuki5, Tak Wah Mak6, Toru Nakano7, Tohru Fushiki3, Junji Takeda1, 8 & Iichiro Shimomura2, 9, 10

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

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

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

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

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

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

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

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

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

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

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.

（2004/10/18　共同通信）