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Submitted on November 10, 2006
Accepted on March 26, 2007
Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy, Göteborg University, Göteborg, Sweden; Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Radiology, the Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
* To whom correspondence should be addressed. E-mail: kajsa.sjoholm{at}medic.gu.se.
Context: We have previously identified NAD(P)H: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 play an important role also in metabolism.
Objective: To explore the expression and regulation of NQO1 in human adipose tissue and isolated adipocytes.
Patients and results: The high expression of NQO1 in adipocytes was verified in human adipocytes and adipose tissue by real-time PCR. DNA microarray analysis showed that NQO1 was expressed at higher levels in large compared to small adipocytes, isolated from the same fat biopsy. Furthermore, NQO1 mRNA levels were positively correlated to adipocyte size (n=7, p<0.002). During an 18 week diet regime, (n=24; mean weight loss 27 kg), the NQO1 expression in human subcutaneous adipose tissue was downregulated (p<0.0001), and mRNA levels correlated to body mass index (p=0.0005), subcutaneous and total abdominal adipose tissue areas as determined by computerized tomography (p<0.0001, both) and metabolic parameters. NQO1 mRNA levels were also positively correlated to aspartate aminotransferase (p=0.0028) and alanine aminotransferase (p=0.0219), markers known to be associated with severity of hepatic steatosis.
Conclusions: NQO1 is highly expressed in human adipose tissue, in particular in large adipocytes. Adipose tissue 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.
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A. Gummesson, M. Jernas, P.-A. Svensson, I. Larsson, C. A. M. Glad, E. Schele, L. Gripeteg, K. Sjoholm, T. C. Lystig, L. Sjostrom, et al. Relations of Adipose Tissue CIDEA Gene Expression to Basal Metabolic Rate, Energy Restriction, and Obesity: Population-Based and Dietary Intervention Studies J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4759 - 4765. [Abstract] [Full Text] [PDF] |
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