Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice
| Autor: | Ken Ichi Yamamura, Yukari Date, Masamitsu Nakazato, Takeyori Saheki, Hiroshi Miki, Junji Kamon, Kajuro Komeda, Hironori Waki, Yasuo Akanuma, Yuichi Oike, Ryozo Nagai, Takeshi Naitoh, Toshimasa Yamauchi, Takashi Kadowaki, Satoshi Kimura, Meng Xian Li, Atsuko Tsuchida |
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| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Heterozygote Lipodystrophy Biology CREB Mice Adipose Tissue Brown Internal medicine Coactivator Genetics medicine Adipocytes Animals RNA Messenger CREB-binding protein Receptor Transcription factor Cell Size Nuclear Proteins CREB-Binding Protein Dietary Fats Mice Mutant Strains Sterol regulatory element-binding protein DNA-Binding Proteins Endocrinology Nuclear receptor Adipose Tissue biology.protein CCAAT-Enhancer-Binding Proteins Trans-Activators Sterol Regulatory Element Binding Protein 1 Insulin Resistance Energy Metabolism Transcription Factors |
| Zdroj: | Nature genetics. 30(2) |
| ISSN: | 1061-4036 |
| Popis: | The CBP protein (cAMP response element binding protein (CREB) binding protein) is a co-activator for several transcription factors with a wide range of important biological functions, such as sterol regulatory element binding proteins (SREBPs), CCAAT/enhancer-binding proteins (C/EBPs), nuclear receptors (including peroxisome proliferator-activated receptors, PPARs), and signal transducers and activators of transcription (STATs). In contrast to these individual transcription factors, the biological roles of CBP are poorly understood. CBP enhances transcriptional activities via histone acetylation and the recruitment of additional co-activators such as SRC (steroid coactivator)-1 (ref. 9). To identify its physiological functions using a loss-of-function mutant, we analyzed CBP-deficient mice. As Crebbp null mice (Crebbp-/-) died during embryogenesis, we used Crebbp+/- mice. Unexpectedly, Crebbp+/- mice showed markedly reduced weight of white adipose tissue (WAT) but not of other tissues. Despite this lipodystrophy, Crebbp+/- mice showed increased insulin sensitivity and glucose tolerance and were completely protected from body weight gain induced by a high-fat (HF) diet. We observed increased leptin sensitivity and increased serum adiponectin levels in Crebbp+/- mice. These increased effects of insulin-sensitizing hormones secreted from WAT may explain, at least in part, the phenotypes of Crebbp+/- mice. This study demonstrates that CBP may function as a 'master-switch' between energy storage and expenditure. |
| Databáze: | OpenAIRE |
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