The expression of NAD(P)H:quinone oxidoreductase 1 is high in human adipose tissue, reduced by weight loss, and correlates with adiposity, insulin sensitivity, and markers of liver dysfunction.
BACKGROUND
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.


OBJECTIVE
The aim of this study was to explore the expression and regulation of NQO1 in human adipose tissue (AT) and isolated adipocytes.


RESULTS
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.


CONCLUSIONS
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.
Palming
Jenny
J
Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Sjöholm
Kajsa
K
Jernås
Margareta
M
Lystig
Theodore C
TC
Gummesson
Anders
A
Romeo
Stefano
S
Lönn
Lars
L
Lönn
Malin
M
Carlsson
Björn
B
Carlsson
Lena M S
LM
D000273:Adipose Tissue / Q000201:enzymology*; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001835:Body Weight / Q000502:physiology; D004038:Diet, Reducing; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000201:enzymology; D008107:Liver Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism*; D009765:Obesity / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D015431:Weight Loss / Q000502:physiology
D015415:Biomarkers; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human