Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism
Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism
复制标题
DOI：
10.1152/ajpendo.00084.2012
复制
发表时间：
2012-08-01
影响因子：
5.1
通讯作者：
Smas, Cynthia M.
中科院分区：
文献类型：
--
作者：
Ren, Gang;Kim, Ji Young;Smas, Cynthia M.
Ren G，Kim JY，Smas CM.一种新的脂肪细胞富集胰岛素靶基因RIFL的鉴定，该基因在脂质代谢中起作用。Am J Physiol Endocrinol Metab 303：E334-E351，2012.首次发表于2012年5月8日; doi：10.1152/ajpendo.00084.2012.-为了鉴定在脂肪代谢中重要的新基因，我们利用了编码跨膜和分泌因子的基因的Lexicon-Genentech敲除数据库以及我们为3 T3-L1体外脂肪形成产生的全鼠基因组转录谱数据。交叉引用无效模型证明代谢表型与脂肪形成诱导的基因导致识别一个新的基因，我们命名为RIFL（再喂养诱导的脂肪和肝脏）。RIFL缺失小鼠的血清甘油三酯水平约为野生型的三分之一。RIFL转录物在3 T3-L1脂肪形成期间被诱导>100倍，并且在鼠和人原代前脂肪细胞的脂肪形成期间也显著增加。在3 T3-L1脂肪形成过程中siRNA介导的RIFL敲低导致脂肪细胞甘油三酯含量降低约35%。鼠RIFL转录物在白色和棕色脂肪组织和肝脏中高度富集。WAT的分级显示RIFL转录物仅在脂肪细胞中表达，在基质血管细胞中缺乏表达。营养和激素研究与RIFL的促脂肪生成功能一致。有证据表明，与野生型小鼠相比，ob/ob小鼠WAT中的RIFL转录水平增加了约8倍。禁食小鼠再喂食后，WAT和肝脏中的RIFL转录物水平分别增加了80倍和12倍。用胰岛素处理3 T3-L1脂肪细胞增加RIFL转录
Ren G, Kim JY, Smas CM. Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism. Am J Physiol Endocrinol Metab 303: E334-E351, 2012. First published May 8, 2012; doi:10.1152/ajpendo.00084.2012.-To identify new genes that are important in fat metabolism, we utilized the Lexicon-Genentech knockout database of genes encoding transmembrane and secreted factors and whole murine genome transcriptional profiling data that we generated for 3T3-L1 in vitro adipogenesis. Cross-referencing null models evidencing metabolic phenotypes with genes induced in adipogenesis led to identification of a new gene, which we named RIFL (refeeding induced fat and liver). RIFL-null mice have serum triglyceride levels approximately one-third of wild type. RIFL transcript is induced >100-fold during 3T3-L1 adipogenesis and is also increased markedly during adipogenesis of murine and human primary preadipocytes. siRNA-mediated knockdown of RIFL during 3T3-L1 adipogenesis results in an similar to 35% decrease in adipocyte triglyceride content. Murine RIFL transcript is highly enriched in white and brown adipose tissue and liver. Fractionation of WAT reveals that RIFL transcript is exclusive to adipocytes with a lack of expression in stromal-vascular cells. Nutritional and hormonal studies are consistent with a prolipogenic function for RIFL. There is evidence of an approximately eightfold increase in RIFL transcript level in WAT in ob/ob mice compared with wild-type mice. RIFL transcript level in WAT and liver is increased similar to 80- and 12-fold, respectively, following refeeding of fasted mice. Treatment of 3T3-L1 adipocytes with insulin increases RIFL transcript