Stimulation of the innate immune receptors Toll-like receptor (TLR)-2 and TLR4 has been shown to promote the development of a variety of diseases involving dysregulated metabolism, including atherosclerosis, type 2 diabetes and non-alcoholic fatty liver disease. However, the origin and nature of the agents responsible for stimulating TLR2 or TLR4 signalling in these conditions remain to be clearly identified. This review summarises the evidence supporting the proposal that 'pathogen-associated molecular patterns' (PAMPs) derived from dietary and commensal sources may contribute to the chronic inflammatory processes that underpin the development of these diseases via stimulation of TLR2 and TLR4. In particular, insights gained from recent studies employing TLR-transfectant based bioassays to quantify the abundance of PAMPs in foodstuffs and specific commensal compartments are discussed. Finally, the major mechanisms by which TLR-stimulants may gain access to the circulation to promote systemic low-grade inflammation are considered.
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