Background and aims: Adipose tissue (AT) secretes cytokines which contribute to systemic inflammation in obesity. Cytokines like monocyte-chemoattractant-protein-1 (MCP-1) have also been associated with macrophage infiltration of AT in obese mice. However, it is unknown whether visceral-AT (VAT) or subcutaneous-AT (SCAT) expression is related to serum levels of these cytokines in humans.
Methods: Morbidly-obese non-diabetic subjects undergoing bariatric surgery (age=44.5±1.4 years (mean±S.E.M.), BMI=46.8±1.9 kg/m2, n=37) and age-matched lean controls undergoing elective surgery (age=42.3±4.1 years, BMI=23.6±0.8 kg/m2, n=18) were recruited. Serum, VAT and SCAT samples were taken from each subject. Serum adipokine and cytokine levels were measured by ELISA and their AT-derived mRNA expression by Real-time multiplex PCR.
Results: Serum hsCRP was positively correlated with serum IL-6 (r=0.57, P<0.001); IL-18 (r=0.42, P=0.001), MCP-1 (r=0.62, P<0.001) and fat mass (FM; r=0.82, P<0.001). Whilst there is no association of serum IL-6 with IL-6VAT expression, serum IL-6 was negatively correlated with IL-6 SCATmRNA expression (r=−0.37, P<0.05). Similarly IL-18 serum levels are not correlated with VATmRNA expression, however, they correlate positively with SCATmRNA expression (r=0.52, P<0.001). However, serum MCP-1 levels are not associated with VAT or SCATmRNA expression, serumMCP-1 correlated with FM (r=0.63, P<0.001) but not HOMA-IR when corrected for fat mass. VAT expression of these cytokines was unrelated with leptinVATmRNA expression or HOMA-IR, only IL-18 VATmRNA correlated with adiponectinVAT when corrected for FM (r=−0.34, P=0.02).
Conclusion: Serum levels of IL-6, IL-18 and MCP-1 correlate with FM and hsCRP. Serum IL-6 and IL-18 correlate with their SCAT expression but are unrelated to VAT expression. In contrast, elevation of MCP-1 appears to be unrelated to AT expression. Serum levels of IL-6 have a reciprocal correlation with SCATmRNA expression, consistent with its lipolytic effects and anti-obesity potential, whilst IL-18 shows a direct correlation. A feedback mechanisms may exist between circulating cytokines and their SCAT expression. Omental fat appears to elicit less feedback, and contribute to circulating cytokines in humans, but its secretory potential remains to be further established.