State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
FEBS J. 2014 May;281(10):2399-409. doi: 10.1111/febs.12792. Epub 2014 Apr 22.
Adipose tissue is crucial for energy homeostasis and is a topic interest with respect to investigating the regulation of adipose tissue formation for the ever-increasing health concerns of obesity and type 2 diabetes. Adipocyte differentiation is tightly regulated by the characteristic sequential expression change of adipocyte genes, including members of the CCATT/enhancer binding protein (C/EBP) family of transcription factors, peroxisome proliferator-activated receptor γ and tribbles homolog 3. In the present study, we demonstrate that C/EBPβ and peroxisome proliferator-activated receptor γ (but not tribbles homolog 3) are targeted for activation by activating transcription factor 4 (ATF4), a member of cAMP response element-binding/activator transcription factor family. Importantly, overexpression of ATF4 in 3T3-L1 cells enhanced adipogenesis, whereas small-interfering ATF4 blocked conversion of preadipocytes to adipocytes. These findings were accomplished by altering the coordinate expression of adipogenic transcription factors. Taken together, our results suggest that ATF4 is a positive regulator of adipocyte differentiation. This notion is also supported by the results of the present study showing that the expression of ATF4 is induced during adipocyte differentiation. Thus, ATF4 could be an important regulator of energy homeostasis.
脂肪组织对于能量平衡至关重要，并且是研究脂肪组织形成调节的一个热门课题，因为肥胖症和 2 型糖尿病的健康问题日益受到关注。脂肪细胞分化受到脂肪细胞基因特征性顺序表达变化的严格调控，包括转录因子 CCATT/增强子结合蛋白（C/EBP）家族成员、过氧化物酶体增殖物激活受体 γ 和 tribbles 同源物 3。在本研究中，我们证明 C/EBPβ 和过氧化物酶体增殖物激活受体 γ（但不是 tribbles 同源物 3）是通过激活转录因子 4（ATF4）被靶向激活的，ATF4 是 cAMP 反应元件结合/激活转录因子家族的成员。重要的是，在 3T3-L1 细胞中过表达 ATF4 增强了脂肪生成，而 ATF4 的小干扰则阻止了前脂肪细胞向脂肪细胞的转化。这些发现是通过改变脂肪生成转录因子的协调表达来实现的。总之，我们的研究结果表明，ATF4 是脂肪细胞分化的正向调节因子。本研究的结果也支持了这一观点，即 ATF4 在脂肪细胞分化过程中表达上调。因此，ATF4 可能是能量平衡的重要调节因子。
