Liu Yang, Maekawa Toshio, Yoshida Keisuke, Furuse Tamio, Kaneda Hideki, Wakana Shigeharu, Ishii Shunsuke
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; Department of Molecular Genetics and Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Biochem Biophys Res Commun. 2016 Sep 16;478(2):696-702. doi: 10.1016/j.bbrc.2016.08.009. Epub 2016 Aug 3.
The activating transcription factor (ATF)2 family of transcription factors regulates a variety of metabolic processes, including adipogenesis and adaptive thermogenesis. ATF7 is a member of the ATF2 family, and mediates epigenetic changes induced by environmental stresses, such as social isolation and pathogen infection. However, the metabolic role of ATF7 remains unknown. The aim of the present study is to examine the role of ATF7 in metabolism using ATF7-dificeint mice. Atf7(-/-) mice exhibited lower body weight and resisted diet-induced obesity. Serum triglycerides, resistin, and adipose tissue mass were all significantly lower in ATF7-deficient mice. Fasting glucose levels and glucose tolerance were unaltered, but systemic insulin sensitivity was increased, by ablation of ATF7. Indirect calorimetry revealed that oxygen consumption by Atf7(-/-) mice was comparable to that of wild-type littermates on a standard chow diet, but increased energy expenditure was observed in Atf7(-/-) mice on a high-fat diet. Hence, ATF7 ablation may impair the development and function of adipose tissue and result in elevated energy expenditure in response to high-fat-feeding obesity and insulin resistance, indicating that ATF7 is a potential therapeutic target for diet-induced obesity and insulin resistance.
转录激活因子（ATF）2家族转录因子调控多种代谢过程，包括脂肪生成和适应性产热。ATF7是ATF2家族的成员，介导由环境应激（如社会隔离和病原体感染）诱导的表观遗传变化。然而，ATF7在代谢中的作用仍不清楚。本研究的目的是使用ATF7基因敲除小鼠来研究ATF7在代谢中的作用。Atf7（-/-）小鼠体重较低，对饮食诱导的肥胖具有抵抗力。ATF7基因敲除小鼠的血清甘油三酯、抵抗素和脂肪组织量均显著降低。通过敲除ATF7，空腹血糖水平和葡萄糖耐量未改变，但全身胰岛素敏感性增加。间接测热法显示，在标准饲料喂养下，Atf7（-/-）小鼠的耗氧量与野生型同窝小鼠相当，但在高脂饮食喂养的Atf7（-/-）小鼠中观察到能量消耗增加。因此，敲除ATF7可能损害脂肪组织的发育和功能，并导致在高脂喂养诱导的肥胖和胰岛素抵抗情况下能量消耗增加，这表明ATF7是饮食诱导的肥胖和胰岛素抵抗的潜在治疗靶点。
