Liver fat content is linked to inflammatory changes in subcutaneous adipose tissue in type 2 diabetes patients

Authors


Correspondence: Henry J. Jansen, Department of Internal Medicine 463, Radboud University Nijmegen Medical Center, PO Box 9101 6500 HB Nijmegen, the Netherlands. Tel.: +31 24 3667203; Fax: +31 24 3540022; E-mail: H.Jansen@aig.umcn.nl

Summary

Background

Patients with type 2 diabetes mellitus (T2DM) are typically overweight and have an increased liver fat content (LFAT). High LFAT may be explained by an increased efflux of free fatty acids from the adipose tissue, which is partly instigated by inflammatory changes. This would imply an association between inflammatory features of the adipose tissue and liver fat content.

Objective

To analyse associations between inflammatory features of the adipose tissue and liver fat content.

Design

A cross-sectional study.

Patients

Twenty-seven obese patients with insulin-treated T2DM were studied.

Measurements

LFAT content was measured by proton magnetic resonance spectroscopy. A subcutaneous (sc) fat biopsy was obtained to determine morphology and protein levels within adipose tissue. In addition to fat cell size, the percentage of macrophages and the presence of crown-like structures (CLSs) within sc fat were assessed by CD68-immunohistochemical staining.

Results

Mean LFAT percentage was 11·1 ± 1·7% (range: 0·75–32·9%); 63% of the patients were diagnosed with an elevated LFAT (upper range of normal ≤5·5%). Whereas adipocyte size did not correlate with LFAT, 3 of 4 subjects with CLSs in sc fat had elevated LFAT and the percentage of macrophages present in sc adipose tissue was positively associated with LFAT. Protein concentrations of adiponectin within adipose tissue negatively correlated with LFAT. Adipose tissue protein levels of the key inflammatory adipokine plasminogen activator inhibitor-1 (PAI-1) were positively associated with LFAT.

Conclusions

Several pro-inflammatory changes in sc adipose tissue associate with increased LFAT content in obese insulin-treated patients with T2DM. These findings suggest that inflammatory changes at the level of the adipose tissue may drive liver fat accumulation.

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