Obesity is associated with a distint inflammatory phenotype in which free fatty acids (FFAs) such as palmitate can elicit the inflammatory cytokines TNF and IL-6 from adipose tissue. In Nature Medicine, Bhattacharya and colleagues demonstrate a key intermediary role for fetuin A (FetA) in obesity-dependent inflammation. FetA is a glycoprotein secreted by the liver and is an important transporter of FFAs. The authors find more FetA in obese patients and show that in vivo knockdown of either FetA or TLR4 diminishes the inflammatory signature in two different experimental models of mouse obesity. FFAs do not bind TLR4 directly but instead do so via FetA. Indeed, the authors confirm FetA-TLR4 binding by both immunoprecipitation and surface plasmon resonance. A complex of FetA and FFA is required for optimal activation of transcrition factor NF-kB proinflammatory cytokine signaling. The output of FetA by the liver therefore has an fundamental influence on the inflammation triggered by FFAs.

Nat. Med. 18, 1279–1285 (2012)