Toll-like receptor stimulants in processed meats promote lipid accumulation in macrophages and atherosclerosis in Apoe−/− mice

Dietary intake of processed meat is a risk factor for cardiovascular disease. However, the effects of processed meats on lipid metabolism in macrophages, a key regulator of cardiovascular risk, have remained largely unexplored. Extracts of processed meats, but not their fresh non-processed equivalents, were found to promote a significant increase in macrophage lipid accumulation in vitro. Calibrated receptor-dependent reporter assays revealed that pro-inflammatory stimulants of Toll-like receptor (TLR)-2 and TLR4 were low or undetectable in fresh meats, but rose dramatically following chopping and storage at 4 °C. Lipid accumulation in response to processed meats correlated well with TLR-stimulant content, was significantly reduced in TLR4-deficient macrophages, and was absent in response to meats stored frozen to prevent bacterial growth. TLR-stimulation significantly increased the incorporation of 14C-acetate into cellular lipids, and induced lipid accumulation in the absence of exogenous lipoproteins, suggesting a key role for de novo lipid synthesis in this process. Aortic atherosclerosis was also significantly accelerated in Apoe−/− mice receiving a diet supplemented with TLR-stimulants at concentrations relevant to those measured in processed meats, compared to normal chow. The findings reveal novel mechanisms which may be of relevance to the observed connections between processed meat consumption, inflammatory markers and cardiovascular risk.