Multiple TLRs, including TLR2, TLR3, TLR4, TLR5, TLR8, TLR9, and TLR10, have been indicated in the regulation of PAMPs from gut microbiota and DAMPs from metabolic stress and tissue damage, which initiate the inflammatory responses contributing to the development of obesity-related chronic diseases (Figure 2). The gene discussed is TLR9; the disease is obesity due to melanocortin 4 receptor deficiency.