Suh Young Ho, Kim Won Ho, Moon Changsuk, Hong Yun Hwa, Eun Su-Yong, Lim Joo Hyun, Choi Joo Sun, Song Jihyun, Jung Myeong Ho
Division of Metabolic Diseases, Department of Biomedical Sciences, National Institute of Health, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2005 Nov 18;337(2):481-9. doi: 10.1016/j.bbrc.2005.09.078. Epub 2005 Sep 21.
Neuronatin (Nnat) is selectively expressed in the neonatal brain and is involved in neuronal differentiation during brain development. However, Nnat also appears to be abundantly expressed in adipose tissue, and is conspicuously elevated in the adipose tissue of obese Zucker diabetic fatty rats compared with control lean Zucker lean control rats shown in our previous report. Here, we examined the expression of Nnat in adipose tissue and demonstrated that the ectopic expression of Nnat mediated by retroviral infection or stable transfection of 3T3-L1 pre-adipocytes stimulated differentiation into mature adipocytes with early induction of adipogenic transcription factors. Moreover, in 3T3-L1 cells overexpressing Nnat, increased intracellular free calcium levels and enhanced phosphorylation of cAMP-response element-binding protein (CREB) were observed, which appears to potentiate CCAAT/enhancer-binding protein (C/EBP)beta, C/EBPdelta, and C/EBPalpha transcriptional activities. Collectively, the data indicate that Nnat enhances CREB phosphorylation through increasing intracellular free calcium levels, which potentiates expression of adipogenic transcription factors resulting in heightened adipocyte differentiation. These findings contribute to a greater fundamental understanding of obesity, a clinically important risk factor in numerous diseases.
神经调节素（Nnat）在新生大脑中选择性表达，并参与大脑发育过程中的神经元分化。然而，Nnat在脂肪组织中似乎也大量表达，并且与我们之前报告中所示的对照瘦型 Zucker 大鼠相比，肥胖的 Zucker 糖尿病脂肪大鼠的脂肪组织中 Nnat 明显升高。在此，我们检测了 Nnat 在脂肪组织中的表达，并证明通过逆转录病毒感染或 3T3-L1 前脂肪细胞的稳定转染介导的 Nnat 异位表达刺激其分化为成熟脂肪细胞，并早期诱导脂肪生成转录因子。此外，在过表达 Nnat 的 3T3-L1 细胞中，观察到细胞内游离钙水平升高以及 cAMP 反应元件结合蛋白（CREB）的磷酸化增强，这似乎增强了CCAAT/增强子结合蛋白（C/EBP）β、C/EBPδ和 C/EBPα的转录活性。总体而言，数据表明 Nnat 通过增加细胞内游离钙水平增强 CREB 磷酸化，这增强了脂肪生成转录因子的表达，导致脂肪细胞分化增强。这些发现有助于更深入地从根本上理解肥胖，肥胖是许多疾病中临床上重要的危险因素。
