Tanaka Masaki, Nozaki Maiko, Fukuhara Atsunori, Segawa Katsumori, Aoki Naohito, Matsuda Morihiro, Komuro Ryutaro, Shimomura Iichiro
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan.
Biochem Biophys Res Commun. 2007 Jul 27;359(2):194-201. doi: 10.1016/j.bbrc.2007.05.096. Epub 2007 May 25.
Visfatin is a secretory protein which exerts insulin mimetic and proinflammatory effects, also functioning as an intracellular enzyme to produce NAD. Plasma visfatin levels and visfatin mRNA expression in adipose tissues are increased in obese subjects. Visfatin does not have a decent cleavable signal sequence, and the mechanism, that mediates release of visfatin from adipocytes, remains poorly understood. In this study, we demonstrate that visfatin is released abundantly into culture medium from 3T3-L1 adipocytes. Subcellular fractionation analysis showed that visfatin was localized in the cytosol, but not in nucleus, membrane, vesicles, or mitochondria fractions. Visfatin release was not reduced by Brefeldin A and Monensin, inhibitors of endoplasmic reticulum (ER)-Golgi-dependent secretion. In addition, visfatin was not released on microvesicles. These results suggest that visfatin should be released from 3T3-L1 adipocytes via an ER-Golgi or microvesicles independent pathway.
内脂素是一种分泌蛋白，具有胰岛素模拟和促炎作用，还作为一种细胞内酶来产生烟酰胺腺嘌呤二核苷酸（NAD）。肥胖受试者的血浆内脂素水平和脂肪组织中的内脂素mRNA表达会升高。内脂素没有合适的可裂解信号序列，介导内脂素从脂肪细胞释放的机制仍知之甚少。在本研究中，我们证明内脂素从3T3-L1脂肪细胞大量释放到培养基中。亚细胞分级分离分析表明，内脂素定位于细胞质中，而不是细胞核、细胞膜、囊泡或线粒体组分中。布雷菲德菌素A和莫能菌素是内质网（ER）-高尔基体依赖性分泌的抑制剂，内脂素的释放不受它们的影响。此外，内脂素不会在微泡上释放。这些结果表明，内脂素应通过独立于ER-高尔基体或微泡的途径从3T3-L1脂肪细胞中释放出来。
