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Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

A Corrigendum to this article was published on 14 June 2010

Abstract

Objective:

Insulin resistance in visceral obesity is substantially driven by adipose tissue inflammation, particularly by macrophages accumulating in obese adipose tissue. In contrast, adipose tissue macrophages express the hemoglobin scavenger receptor (CD163) and heme oxygenase-1 (gene: HMOX1) that together protect from oxidative stress. Our aim was to evaluate the expression of CD163 and HMOX1 in intra-abdominal visceral (omental) and subcutaneous adipose tissue as well as circulating soluble CD163 concentrations in human obesity and its association with adipose tissue inflammation, body fat distribution and insulin resistance.

Methods:

CD163, HMOX1 and CD68 mRNA expression in visceral and subcutaneous adipose tissue, serum concentration of soluble CD163 in morbidly obese patients (body mass index (BMI) >40 kg m−2), who underwent laparoscopic surgery for gastric banding (n=20), matched for age and sex to controls (BMI<30 kg m−2; n=20) was analyzed.

Results:

CD163 expression was highly upregulated in human adipose tissue and soluble CD163 serum concentration was elevated in obese vs lean subjects. HMOX1 was upregulated in adipose tissue by obesity as well and expressed predominantly in macrophages. Although CD163 expression strictly correlated with macrophage abundance, HMOX1 was additionally upregulated within macrophages. This upregulation was significantly lower in visceral compared with subcutaneous adipose tissue. Strikingly, relative visceral adipose tissue expression of HMOX1 negatively correlated with waist-to-hip ratio and the homeostasis model assessment of insulin resistance (both P=0.024).

Conclusions:

Visceral obesity is associated with defective upregulation of heme oxygenase-1 in visceral adipose tissue. A lack of this antioxidative and anti-inflammatory enzyme in visceral adipose tissue could contribute to the development of insulin resistance.

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Acknowledgements

The research leading to these results has received funding from the European Community's 7th Framework Programme (FP7/2007–2013) under grant agreement no. 201608, from the Austrian Science Fund (project no. P18776-B11), and the Austrian National Bank (project no. 12735; all to TMS).

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Correspondence to T M Stulnig.

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Shakeri-Manesch, S., Zeyda, M., Huber, J. et al. Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance. Int J Obes 33, 1257–1264 (2009). https://doi.org/10.1038/ijo.2009.160

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