Klöting Nora, Graham Timothy E, Berndt Janin, Kralisch Susan, Kovacs Peter, Wason Christopher J, Fasshauer Mathias, Schön Michael R, Stumvoll Michael, Blüher Matthias, Kahn Barbara B
Department of Internal Medicine III, University of Leipzig, D-04103 Leipzig, Germany.
Cell Metab. 2007 Jul;6(1):79-87. doi: 10.1016/j.cmet.2007.06.002.
Intra-abdominal fat is associated with insulin resistance and cardiovascular risk. Levels of serum retinol-binding protein (RBP4), secreted by fat and liver cells, are increased in obesity and type 2 diabetes (T2D). Here we report that, in 196 subjects, RBP4 is preferentially expressed in visceral (Vis) versus subcutaneous (SC) fat. Vis fat RBP4 mRNA was increased approximately 60-fold and 12-fold in Vis and SC obese subjects respectively versus lean subjects, and approximately 2-fold with impaired glucose tolerance/T2D subjects versus normoglycemic subjects. In obese subjects, serum RBP4 was increased 2- to 3-fold, and serum transthyretin, which stabilizes RBP4 in the circulation, was increased 35%. Serum RBP4 correlated positively with adipose RBP4 mRNA and intra-abdominal fat mass and inversely with insulin sensitivity, independently of age, gender, and body mass index. RBP4 mRNA correlated inversely with GLUT4 mRNA in Vis fat and positively with adipocyte size in both depots. RBP4 levels are therefore linked to Vis adiposity, and Vis fat may be a major source of RBP4 in insulin-resistant states.
腹部脂肪与胰岛素抵抗及心血管风险相关。脂肪细胞和肝细胞分泌的血清视黄醇结合蛋白（RBP4）水平在肥胖和2型糖尿病（T2D）患者中升高。在此我们报告，在196名受试者中，RBP4在内脏脂肪（Vis）中相较于皮下脂肪（SC）优先表达。与瘦人相比，Vis和SC肥胖受试者的Vis脂肪RBP4 mRNA分别增加了约60倍和12倍；与血糖正常的受试者相比，糖耐量受损/T2D受试者的Vis脂肪RBP4 mRNA增加了约2倍。在肥胖受试者中，血清RBP4增加了2至3倍，而在循环中稳定RBP4的血清转甲状腺素蛋白增加了35%。血清RBP4与脂肪组织RBP4 mRNA及腹部脂肪量呈正相关，与胰岛素敏感性呈负相关，且不受年龄、性别和体重指数的影响。RBP4 mRNA在Vis脂肪中与葡萄糖转运蛋白4（GLUT4）mRNA呈负相关，在两个脂肪库中均与脂肪细胞大小呈正相关。因此，RBP4水平与Vis肥胖相关，在胰岛素抵抗状态下，Vis脂肪可能是RBP4的主要来源。
