Stefan Norbert, Hennige Anita M, Staiger Harald, Machann Jürgen, Schick Fritz, Schleicher Erwin, Fritsche Andreas, Häring Hans-Ulrich
Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, D-72076 Tübingen, Germany.
Diabetes Care. 2007 May;30(5):1173-8. doi: 10.2337/dc06-2342. Epub 2007 Jan 26.
Retinol-binding protein 4 (RBP4) is an adipokine that induced insulin resistance in mice, and high plasma RBP4 levels were associated with insulin-resistant states in humans. To determine which fat compartments are associated with elevated RBP4 levels in humans, we measured circulating RBP4 in 75 healthy subjects and used state-of-the-art measurements of body fat distribution.
Total body, visceral, and subcutaneous abdominal fat were determined by magnetic resonance tomography and liver fat and intramyocellular fat by localized proton magnetic resonance spectroscopy. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp and, together with insulin clearance, estimated from the oral glucose tolerance test (OGTT).
Adjusted circulating RBP4 correlated negatively with insulin sensitivity (clamp: r = -0.33, P = 0.005; OGTT: r = -0.36, P = 0.002) and positively with parameters in the fasting state as insulin levels (r = 0.35, P = 0.003) and homeostasis model assessment of insulin resistance (r = 0.34, P = 0.004). In addition, circulating RBP4 correlated negatively with hepatic insulin clearance (r = -0.25, P = 0.04). Circulating RBP4 was not associated with total body, visceral, or subcutaneous abdominal fat (all P > or = 0.29). Plasma RBP4 levels were also not associated with intramyocellular fat or circulating adiponectin or leptin. In contrast, plasma RBP4 levels correlated positively with liver fat in cross-sectional (r = 0.27, P = 0.03) and longitudinal (r = 0.37, P = 0.04) analyses.
Circulating RBP4 is not associated with the amount of fat in the classical depots or in the ectopic depots in muscle. However, it correlates positively with liver fat. Furthermore, metabolic parameters support the close relationship between circulating RBP4 with liver fat and, presumably, hepatic insulin resistance.
视黄醇结合蛋白4（RBP4）是一种脂肪因子，可诱导小鼠产生胰岛素抵抗，而血浆RBP4水平升高与人类胰岛素抵抗状态相关。为了确定人体中哪些脂肪组织与RBP4水平升高有关，我们测量了75名健康受试者的循环RBP4，并采用了最先进的身体脂肪分布测量方法。
通过磁共振断层扫描确定全身、内脏和腹部皮下脂肪，通过局部质子磁共振波谱测定肝脏脂肪和肌内脂肪。通过正常血糖高胰岛素钳夹技术测量胰岛素敏感性，并根据口服葡萄糖耐量试验（OGTT）估计胰岛素清除率。
校正后的循环RBP4与胰岛素敏感性呈负相关（钳夹：r = -0.33，P = 0.005；OGTT：r = -0.36，P = 0.002），与空腹状态下的参数如胰岛素水平（r = 0.35，P = 0.003）和胰岛素抵抗的稳态模型评估（r = 0.34，P = 0.004）呈正相关。此外，循环RBP4与肝脏胰岛素清除率呈负相关（r = -0.25，P = 0.04）。循环RBP4与全身、内脏或腹部皮下脂肪均无关联（所有P≥0.29）。血浆RBP4水平也与肌内脂肪、循环脂联素或瘦素无关。相反，在横断面分析（r = 0.27，P = 0.03）和纵向分析（r = 0.37，P = 0.04）中，血浆RBP4水平与肝脏脂肪呈正相关。
循环RBP4与经典脂肪库或肌肉异位脂肪库中的脂肪量无关。然而，它与肝脏脂肪呈正相关。此外，代谢参数支持循环RBP4与肝脏脂肪以及可能的肝脏胰岛素抵抗之间的密切关系。
