Six-transmembrane epithelial antigen of prostate 4 and neutrophil gelatinase-associated lipocalin expression in visceral adipose tissue is related to iron status and inflammation in human obesity
Six-transmembrane epithelial antigen of prostate 4 and neutrophil gelatinase-associated lipocalin expression in visceral adipose tissue is related to iron status and inflammation in human obesity
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DOI：
10.1007/s00394-012-0464-8
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发表时间：
2013-09-01
影响因子：
5
通讯作者：
Fruehbeck, Gema
中科院分区：
文献类型：
--
作者：
Catalan, Victoria;Gomez-Ambrosi, Javier;Fruehbeck, Gema
前列腺六跨膜上皮抗原（STEAP）-4和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是与铁稳态相关的新型脂肪因子，在胰岛素抵抗和炎症中具有潜在作用。本研究的目的是评估肥胖和铁营养状况对内脏脂肪组织（VAT）中STEAP-4和NGAL基因表达水平的影响及其在炎症中的意义。进行实时PCR和Western印迹以定量VAT中STEAP 4和NGAL的水平以及与炎症途径中涉及的其他基因的关联。与瘦型受试者相比，肥胖患者STEAP 4和NGAL mRNA表达水平显著升高（P < 0.001）。NGAL（P < 0.05）和STEAP 4的蛋白表达水平在肥胖患者的内脏脂肪库中也更高，尽管STEAP 4的蛋白水平没有达到统计学显著性。经体脂（BF）调节后，STEAP 4和NGAL基因表达水平与游离铁浓度呈负相关（P < 0.05），而NGAL mRNA与循环铁蛋白浓度呈正相关（P <0.05）。STEAP 4和NGAL基因表达水平与炎症标志物之间存在显著正相关（P < 0.01），首次发现人VAT中STEAP 4和NGAL mRNA和蛋白水平与铁营养状况相关。此外，STEAP 4和NGAL与促炎标志物相关，表明它们可能参与伴随肥胖的低度慢性炎症。
Six-transmembrane epithelial antigen of prostate (STEAP)-4 and neutrophil gelatinase-associated lipocalin (NGAL) are novel adipokines related to iron homeostasis with potential roles in insulin resistance and inflammation. The aim of the present work was to evaluate the effect of obesity and iron status on gene expression levels of STEAP-4 and NGAL in visceral adipose tissue (VAT) and its implication in inflammation.VAT biopsies obtained from 53 subjects were used in the study. Real-time PCR and Western-blot were performed to quantify the levels of STEAP4 and NGAL in VAT as well as the association with other genes implicated in inflammatory pathways. Circulating ferritin and free iron concentrations were also determined.Obese patients exhibited significantly increased STEAP4 and NGAL mRNA expression levels (P < 0.001) compared to lean subjects. Protein expression levels of NGAL (P < 0.05) and STEAP4 were also higher in the visceral fat depot of obese patients, although protein levels of STEAP4 did not reach statistical significance. A negative correlation (P < 0.05) between free iron concentrations and gene expression levels of both STEAP4 and NGAL was found, while circulating ferritin concentrations were positively correlated (P < 0.05) with NGAL mRNA after body fat (BF) adjustment. Furthermore, a significant positive association between STEAP4 and NGAL gene expression levels with inflammatory markers was also detected (P < 0.01).These findings represent the first observation that STEAP4 and NGAL mRNA and protein levels in human VAT are related to iron status. Moreover, STEAP4 and NGAL are associated with pro-inflammatory markers suggesting their potential involvement in the low-grade chronic inflammation accompanying obesity.