Yao-Borengasser Aiwei, Varma Vijayalakshmi, Bodles Angela M, Rasouli Neda, Phanavanh Bounleut, Lee Mi-Jeong, Starks Tasha, Kern Leslie M, Spencer Horace J, Rashidi Amir Adel, McGehee Robert E, Fried Susan K, Kern Philip A
The Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA.
J Clin Endocrinol Metab. 2007 Jul;92(7):2590-7. doi: 10.1210/jc.2006-0816. Epub 2007 Jun 26.
Retinol binding protein 4 (RBP4) was recently found to be expressed and secreted by adipose tissue, and was strongly associated with insulin resistance.
The aim was to determine the relationship between RBP4 and obesity, insulin resistance, and other markers of insulin resistance in humans.
RBP4 mRNA levels in adipose tissue and muscle of nondiabetic human subjects with either normal or impaired glucose tolerance (IGT) were studied, along with plasma RBP4. RBP4 gene expression was also measured in adipose tissue fractions, and from visceral and sc adipose tissue (SAT) from surgical patients.
The study was conducted at University Hospital and General Clinical Research Center.
Insulin sensitivity (S(I)) was measured, and fat and muscle biopsies were performed. In IGT subjects, these procedures were performed before and after treatment with metformin or pioglitazone.
The relationship between RBP4 expression and obesity, S(I), adipose tissue inflammation, and intramyocellular lipid level, and response to insulin sensitizers was measured.
RBP4 was expressed predominantly from the adipocyte fraction of SAT. Although SAT RBP4 expression and the plasma RBP4 level demonstrated no significant relationship with body mass index or S(I), there was a strong positive correlation between RBP4 mRNA and adipose inflammation (monocyte chemoattractant protein-1 and CD68), and glucose transporter 4 mRNA. Treatment of IGT subjects with pioglitazone resulted in an increase in S(I) and an increase in RBP4 gene expression in both adipose tissue and muscle, but not in plasma RBP4 level, and the in vitro treatment of cultured adipocytes with pioglitazone yielded a similar increase in RBP4 mRNA.
RBP4 gene expression in humans is associated with inflammatory markers, but not with insulin resistance. The increase in RBP4 mRNA after pioglitazone treatment is unusual, suggesting a complex regulation of this novel adipokine.
视黄醇结合蛋白4(RBP4)最近被发现由脂肪组织表达并分泌,且与胰岛素抵抗密切相关。
旨在确定RBP4与人类肥胖、胰岛素抵抗及其他胰岛素抵抗标志物之间的关系。
研究了糖耐量正常或受损(IGT)的非糖尿病人类受试者脂肪组织和肌肉中的RBP4 mRNA水平以及血浆RBP4水平。还测量了脂肪组织各部分以及手术患者内脏和皮下脂肪组织(SAT)中的RBP4基因表达。
该研究在大学医院和综合临床研究中心进行。
测量胰岛素敏感性(S(I)),并进行脂肪和肌肉活检。对于IGT受试者,在使用二甲双胍或吡格列酮治疗前后进行这些操作。
测量RBP4表达与肥胖、S(I)、脂肪组织炎症和细胞内脂质水平之间的关系,以及对胰岛素增敏剂的反应。
RBP4主要在SAT的脂肪细胞部分表达。尽管SAT中RBP4表达和血浆RBP4水平与体重指数或S(I)无显著关系,但RBP4 mRNA与脂肪炎症(单核细胞趋化蛋白-1和CD68)以及葡萄糖转运蛋白4 mRNA之间存在强正相关。用吡格列酮治疗IGT受试者导致S(I)增加,脂肪组织和肌肉中RBP4基因表达增加,但血浆RBP4水平未增加,用吡格列酮体外处理培养的脂肪细胞也使RBP4 mRNA有类似增加。
人类RBP4基因表达与炎症标志物相关,但与胰岛素抵抗无关。吡格列酮治疗后RBP4 mRNA增加不寻常,提示这种新型脂肪因子的调节复杂。