Palming Jenny, Sjöholm Kajsa, Jernås Margareta, Lystig Theodore C, Gummesson Anders, Romeo Stefano, Lönn Lars, Lönn Malin, Carlsson Björn, Carlsson Lena M S
Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
J Clin Endocrinol Metab. 2007 Jun;92(6):2346-52. doi: 10.1210/jc.2006-2476. Epub 2007 Apr 3.
We have previously identified nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1 (NQO1), an enzyme involved in the protection against oxidative stress, as a gene predominantly expressed in human adipocytes. Studies in mice deficient in NQO1 activity suggest that NQO1 may also play an important role in metabolism.
The aim of this study was to explore the expression and regulation of NQO1 in human adipose tissue (AT) and isolated adipocytes.
The high expression of NQO1 in adipocytes was verified in human adipocytes and AT by real-time PCR. DNA microarray analysis showed that NQO1 was expressed at higher levels in large compared with small adipocytes, isolated from the same fat biopsy. Furthermore, NQO1 mRNA levels were positively correlated with adipocyte size (n = 7; P < 0.002). During an 18-wk diet regime (n = 24; mean weight loss 27 kg), the NQO1 expression in human sc AT was down-regulated (P < 0.0001), and mRNA levels correlated with body mass index (P = 0.0005), sc, and total abdominal AT areas, as determined by computerized tomography (P < 0.0001, both) and metabolic parameters. NQO1 mRNA levels were also positively correlated with aspartate aminotransferase (P = 0.0028) and alanine aminotransferase (P = 0.0219), markers known to be associated with severity of hepatic steatosis.
NQO1 is highly expressed in human AT, particularly in large adipocytes. AT NQO1 expression is reduced during diet-induced weight loss, and the expression levels positively correlate with adiposity, glucose tolerance, and markers of liver dysfunction. Together, these findings indicate a role for NQO1 in the metabolic complications of human obesity.
我们之前已鉴定出烟酰胺腺嘌呤二核苷酸磷酸醌氧化还原酶1（NQO1），一种参与抗氧化应激保护的酶，作为主要在人类脂肪细胞中表达的基因。对缺乏NQO1活性的小鼠的研究表明，NQO1在代谢中可能也起重要作用。
本研究旨在探讨NQO1在人脂肪组织（AT）和分离的脂肪细胞中的表达及调控。
通过实时PCR在人脂肪细胞和AT中验证了NQO1在脂肪细胞中的高表达。DNA微阵列分析显示，与从同一脂肪活检中分离出的小脂肪细胞相比，大脂肪细胞中NQO1的表达水平更高。此外，NQO1 mRNA水平与脂肪细胞大小呈正相关（n = 7；P < 0.002）。在为期18周的饮食方案期间（n = 24；平均体重减轻27 kg），人皮下AT中NQO1的表达下调（P < 0.0001），mRNA水平与体重指数（P = 0.0005）、皮下及腹部总AT面积相关，通过计算机断层扫描测定（两者均P < 0.0001）以及代谢参数。NQO1 mRNA水平也与天冬氨酸转氨酶（P = 0.0028）和丙氨酸转氨酶（P = 0.0219）呈正相关，这两种标志物已知与肝脂肪变性的严重程度相关。
NQO1在人AT中高表达，尤其是在大脂肪细胞中。饮食诱导体重减轻期间，AT NQO1表达降低，且表达水平与肥胖、葡萄糖耐量及肝功能障碍标志物呈正相关。总之，这些发现表明NQO1在人类肥胖的代谢并发症中起作用。
