Abstract and Introduction
Abstract
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.
Introduction
Most patients with T2DM are obese and have an accumulation of abdominal fat Additionally, liver fat content (LFAT) is strongly associated with intra-abdominal fat mass and clearly increased in subjects with type 2 diabetes. The exact mechanisms involved in liver fat accumulation are currently unclear. It has been suggested that adipose tissue dysfunction is associated with the development of hepatic steatosis, yet data that link liver fat content to adipose tissue inflammation are scarce.
Adipose tissue expansion and adipocyte hypertrophy lead to inflammation as manifested by the infiltration of macrophages. Macrophages can reside in different forms in adipose tissue, but especially an arrangement in so called crown-like structures surrounding adipocytes is viewed as a strong indicator of local inflammation. The pro-inflammatory status of the adipose tissue is further characterized by the increased production of various adipokines including TNFα, IL-6, MCP-1 and PAI-1 and has been linked to the development of insulin resistance. Peripheral insulin resistance promotes the release of fatty acids (FFAs) from adipose tissue that are subsequently taken up by hepatocytes to drive hepatic triglyceride synthesis and accumulation.
Therefore, LFAT content may particularly be increased in patients with T2DM in whom abdominal adipose tissue shows inflammatory traits. This hypothesis was tested in the present study, where we studied inflammatory characteristics of adipose tissue (adipocyte morphology, macrophage influx, the presence of crown-like structures and adipose tissue protein levels of various markers of adipocyte function) in a group of patients with T2DM and investigated whether these markers were associated with liver fat content.