Although triglyceride-rich particles, such as very low-density lipoprotein (VLDL), contribute significantly to human atherogenesis, the molecular basis for lipoprotein-driven pathogenicity is poorly understood. We demonstrate that in macrophages, VLDL functions as a transcriptional regulator via the activation of the nuclear receptor peroxisome proliferator-activated receptor δ. The signaling components of native VLDL are its triglycerides, whose activity is enhanced by lipoprotein lipase. Generation of peroxisome proliferator-activated receptor δ null macrophages verifies the absolute requirement of this transcription factor in mediating the VLDL response. Thus, our data reveal a pathway through which dietary triglycerides and VLDL can directly regulate gene expression in atherosclerotic lesions.
Chawla, A., Lee, C. H., Barak, Y., He, W., Rosenfeld, J., Liao, D., … Evans, R. M. (2003). PPARδ is a very low-density lipoprotein sensor in macrophages. Proceedings of the National Academy of Sciences of the United States of America, 100(3), 1268–1273. https://doi.org/10.1073/pnas.0337331100