Background: Adipose-tissue (AT)-derived cytokines contribute to systemic inflammation and insulin resistance. The systemic inflammation observed in obesity is thought to be mainly derived from the stromavascular fraction of adipose tissue due to macrophage-infiltration of AT in obesity. Macrophages are thought to be recruited and trapped in AT by release of chemoattractant-molecules such as monocyte-chemoattractant-protein-1 (MCP-1) and macrophage-migration-inhibitory-factor (MMIF) which are secreted by adipocytes and AT-stroma-cells. Little is known about the depot-specific-regulation of these chemokines and their relation to human AT-macrophages which differ from rodent macrophages and express CD14.
Methods: A fasting blood sample, visceral-AT (VAT) and subcutaneous-abdominal-AT (SCAT)-biopsies were obtained from 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). Chemokine plasma levels were determined by ELISA and AT-derived mRNA expression by quantitative real-time-PCR.
Results: Plasma-TNFalpha (r=0.5, P<0.001) and VAT-TNFalpha (r=0.35, P<0.01) showed a stronger association to hsCRP than SCAT-TNFalpha (r=0.13, P<0.05). Plasma-TNF-alpha was correlated to circulating-CD14 (r=0.43, P<0.001), but AT-TNFalpha, MMIF and MCP-1 were unrelated to AT-CD14. AT-TNFalpha was correlated to MMIF-expression (VAT: r=0.37, P<0.01; SCAT: r=0.38, P<0.001) but not MCP-1. VAT-MMIF but not SCAT-MMIF correlated with FM (r=0.28, P<0.01), hsCRP (r=0.35, P<0.01) and HOMA-IR (r=0.2, P<0.05) independent of FM. In contrast, AT-MCP-1 was unrelated to hsCRP or HOMA-IR and showed higher expression in SCAT (P<0.001).
Conclusion: We confirmed a close relationship of TNFalpha with AT-MMIF expression but not MCP-1 expression. VAT-MMIF is related to systemic-inflammation and HOMA-IR supporting a role for VAT in the pathogenesis of the metabolic-syndrome. Whilst CD14 expression was not related to systemic inflammation or chemoattractant expression, the characteristics of AT-macrophages differ amongst species and CD14 may not be a reliable marker of AT-macrophage infiltration in humans. MMIF may have a more important role in obesity induced AT-inflammation than MCP-1.