Plasma fetuin-A triggers inflammatory changes in macrophages and adipocytes by acting as an adaptor protein between NEFA and TLR-4

Excerpt

To the Editor: We read with interest the research letter entitled ‘Plasma fetuin-A does not correlate with monocyte TLR4 in humans’ by Jialal and colleagues [1]. The authors state that: ‘Studies using animal models, largely the work of Pal et al [2], have elegantly demonstrated that fetuin-A is the endogenous ligand for Toll-like receptor 4 (TLR4) via which lipids such as fatty acids induce insulin resistance, but there are no data in support of this in humans’. This is not, in fact, the case: in the paper referred to [2], our group provided data on human adipocytes from both diabetic and non-diabetic participants showing that fetuin-A acts as an endogenous ligand of TLR4 to induce insulin resistance. In another recent review, Stefan and Häring observed a significant correlation between circulating fetuin A and insulin resistance in humans [3]. …