Abstract
BackgroundAllograft inflammatory factor 1 (AIF-1) is a putative obesity gene. Our aim was to examine the expression of AIF-1 in human white adipose tissue (WAT) in relation to obesity and metabolic phenotypes in women.MethodsWAT secretion of AIF-1 was determined in subcutaneous adipose tissue pieces in vitro by ELISA from 5 subjects. mRNA expression of AIF-1 was determined by RT-qPCR in the isolated cell fractions of adipose tissue (n = 5-6 per group), in subcutaneous and visceral WAT pieces from non-obese (n = 12) and obese women (n = 23), and in some subcutaneous WAT also before and after weight reduction (n = 10). Finally, adipose AIF-1 mRNA was related to metabolic phenotypes in 96 subjects with a wide range of BMI.ResultsAIF-1 was secreted in a time dependent fashion from WAT. The major source of AIF-1 was WAT resident macrophages. Expression of AIF-1 was similar in visceral and subcutaneous WAT and was two-fold increased in obese women (P < 0.01). AIF-1 mRNA expression levels were normalized after weight reduction (P < 0.01). Expression of AIF-1 was inversely correlated with insulin sensitivity as assessed by insulin tolerance test (KITT), and circulating levels of adiponectin (P = 0.02), and positively correlated with insulin resistance as estimated by HOMA (=0.0042).ConclusionsAIF-1 is a novel adipokine produced mainly by macrophages within human WAT. Its expression is increased in obese women and associates with unfavourable metabolic phenotypes. AIF-1 may play a paracrine role in the regulation of WAT function through cross-talk between macrophages and other cell types within the adipose tissue.
Highlights
Allograft inflammatory factor 1 (AIF-1) is a putative obesity gene
Allograft-inflammatory factor (AIF)-1 is secreted from pieces of adipose tissue We first wanted to assess whether AIF-1 was secreted from human adipose tissue
AIF-1 levels accumulated in the media along the 3 h-experimental period (Figure 1) demonstrating that AIF-1 was secreted in a time dependent-manner from white adipose tissue (WAT) pieces in all of the 5 experiments
Summary
Our aim was to examine the expression of AIF-1 in human white adipose tissue (WAT) in relation to obesity and metabolic phenotypes in women. Dysfunctional adipose tissue is believed to contribute to metabolic disturbances including insulin resistance. “Harmful” adipose tissue is characterized by hypertrophic large fat cells, increased lipolysis, low grade inflammation, and altered release of adipose hormons i.e. adipokines [1,2,3,4]. Obesity is associated with infiltration of activated macrophages in adipose tissue, which besides contributing to insulin resistance [4,7] may be directly involved in regulation of fat mass [8]. Adipose tissue macrophages produce a number of pro-inflammatory cytokines that promote adipose dysfunction and insulin-resistance [4,7]. A number of cytokines have been described to be secreted from different cells in human adipose tissue [9,10]
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