TLR4 and metabolic disease: In metabolic disorders, various ligands activate TLR4: (i) exogenous lipopolysaccharides elevated in serum (Cani et al, 2007), (ii) endogenous damage‐associated molecular patterns (DAMPs), e.g., high‐mobility group box‐1 protein (HMGB1; Harris et al, 2012; Guzmán‐Ruiz et al, 2014), free fatty acids (FFAs; Shi et al, 2006), and fetuin‐A protein (Pal et al, 2012), which are released from macrophages and adipose tissue.