Aims: Emerging data indicate that an impaired release of adipose tissue-derived adipokines could play a pivotal role in the development of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate whether circulating levels or visceral adipose tissue (VAT) expression of recently described adipokines associate with the histopathological disease severity and thus may contribute to the progression of pure fatty liver into an inflammatory and insulin resistant NASH status.
Methods: Serum levels of omentin, chemerin, monocyte chemoattractant protein-1 (MCP-1) and Secreted frizzled-related protein (Sfrp) 4 were measured using enzyme-linked immunosorbent assay (ELISA) in 81 obese patients with biopsy-proven NAFLD and 18 lean control subjects. Expression of the adipokines in VAT was measured using real-time PCR analysis and histopathological grading of NAFLD was scored using the NAFLD activity score (NAS) as verified by Brunt et al.
Results: While VAT expression of omentin and Sfrp 4 (P=0.043 and P<0.001; respectively) as well as serum levels of chemerin (P=0.020) were higher in NAFLD patients compared to controls, adipokine levels did not differ when NAFLD patients were subdivided into groups with simple steatosis, borderline NASH and NASH. Although BMI was similar among NAFLD subgroups, NAS was associated with HOMA-IR independent of age and BMI (β=0.282; P=0.020). Serum adipokine levels were associated neither with histopathological disease severity, nor with their VAT expression. Chemerin VAT expression however, was negatively associated with NAS (r=−0.331, P=0.022) and steatosis score (r=−0.335, P=0.020). Importantly, these associations remained significant when adjusting for age, BMI and HOMA-IR. Furthermore, chemerin VAT expression was significantly lower in patients with moderate or severe steatosis (>33%) versus patients with mild steatosis (<33%; P=0.016).
Conclusion: These findings suggest a protective role of locally distributed VAT-derived chemerin during the pathophysiology of hepatic steatosis and confirm the pivotal role of insulin resistance in NAFLD.