Department of Diabetes and Vascular Medicine, Peninsula Medical School, University of Exeter, Exeter, UK.
Clin Endocrinol (Oxf). 2011 Feb;74(2):197-205. doi: 10.1111/j.1365-2265.2010.03892.x.
The role of retinol-binding protein-4 (RBP4) in human insulin resistance remains controversial, which may in part be explained by a gender-specific secretion of RBP4 in adipose tissue (AT). The aim of the study was to determine gender-specific depot expression of RBP4 and to identify metabolic parameters and cytokines/adipokines associated with RBP4.
The study is an ex-vivo prospective analysis of paired AT-samples from 22 men and 26 women of similar age [men: 43·4 ± 13 (mean ± SD)years, women: 44·1 ± 12 years], BMI (men: 41·9 ± 18kg/m(2) , women: 38·4 ± 11kg/m(2) ) and homeostasis model assessment of insulin resistance taken during elective surgery and ex-vivo culture using visceral-AT (VAT)-explants (n = 10). Plasma RBP4 and cytokines were measured by ELISA and mRNA expression in AT by real-time PCR. VAT-explants were cultured with recombinant leptin and insulin and RBP4 determined by western blot analyses.
Overall subcutaneous AT (SCAT)-RBP4 mRNA expression was higher than VAT-expression [3·1 ± 0·26 signal units (SU; mean ± SE) vs 1·79 ± 0·18SU, n = 48, P < 0·0001], but neither correlated with circulating RBP4. SCAT-RBP4 expression was higher in women and correlated with BMI (r =-0·5, P = 0·009) and fat mass (r= -0·5, P = 0·002). VAT-RBP4 correlated positively with GLUT-4 expression and adiponectin in men only (r= 0·54, P = 0·03 and r = 0·64, P < 0·002, respectively) when correcting for age and fat mass. Multiple regression determined leptin AT-expression as a positive predictor of AT-RBP4 in women (SCAT: β = 0·50, P = 0·002; VAT: β = 0·58, P = 0·003) and adiponectin for VAT-RBP4 in men (β = 0·69; P=0·001). AT-RBP4 mRNA expression showed no relation with insulin resistance. Leptin stimulated RBP-4 secretion ex-vivo, whilst insulin did not affect RBP4.
AT-derived RBP4-mRNA expression is gender specific and regulated by leptin. Circulating RBP4 levels appear to be independent of AT-RBP4 secretion.
视黄醇结合蛋白 4（RBP4）在人体胰岛素抵抗中的作用仍存在争议，这在一定程度上可以解释为脂肪组织（AT）中 RBP4 的性别特异性分泌。本研究旨在确定 RBP4 的性别特异性储存表达，并确定与 RBP4 相关的代谢参数和细胞因子/脂肪因子。
这是一项体外前瞻性分析，对 22 名男性和 26 名年龄相仿（男性：43.4 ± 13 岁，女性：44.1 ± 12 岁）、BMI（男性：41.9 ± 18kg/m2，女性：38.4 ± 11kg/m2）和稳态模型评估胰岛素抵抗的男性和女性的配对 AT 样本进行分析，这些样本是在择期手术期间采集的，并通过内脏脂肪组织（VAT）-外植体（n = 10）进行体外培养。通过 ELISA 测量血浆 RBP4 和细胞因子，通过实时 PCR 测量 AT 中的 mRNA 表达。用重组瘦素和胰岛素培养 VAT 外植体，并通过 Western blot 分析测定 RBP4。
总体而言，皮下脂肪组织（SCAT）-RBP4 mRNA 表达高于 VAT 表达[3.1 ± 0.26 信号单位（SU；平均值 ± SE）与 1.79 ± 0.18SU，n = 48，P < 0.0001]，但与循环 RBP4 均无相关性。女性的 SCAT-RBP4 表达更高，与 BMI（r =-0.5，P = 0.009）和脂肪量（r=-0.5，P = 0.002）相关。仅在男性中，VAT-RBP4 与 GLUT-4 表达和脂联素呈正相关（r = 0.54，P = 0.03 和 r = 0.64，P < 0.002），在校正年龄和脂肪量后。多元回归确定瘦素 AT 表达是女性 AT-RBP4 的正预测因子（SCAT：β = 0.50，P = 0.002；VAT：β = 0.58，P = 0.003），而脂联素是男性 VAT-RBP4 的正预测因子（β = 0.69；P = 0.001）。AT-RBP4 mRNA 表达与胰岛素抵抗无关。瘦素在体外刺激 RBP-4 分泌，而胰岛素则不影响 RBP4。
AT 来源的 RBP4-mRNA 表达具有性别特异性，受瘦素调节。循环 RBP4 水平似乎与 AT-RBP4 分泌无关。
