Title

PPARdelta is a very low-density lipoprotein sensor in macrophages.

Document Type

Article

Publication Date

2003

Keywords

Alleles, Animal, Blotting-Northern, Dose-Response-Relationship-Drug, Flow-Cytometry, Genes-Reporter, Genetic-Vectors, Lipids, Lipoproteins-VLDL, Macrophages, Mice, Models-Genetic, Oxygen, Point-Mutation, Promoter-Regions-(Genetics), Receptors-Cytoplasmic-and-Nuclear, Signal-Transduction, Time-Factors, Transcription-Factors, Transcription-Genetic, Transfection

JAX Source

Proc Natl Acad Sci U S A 2003 Feb; 100(3):1268-73.

Abstract

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 delta. The signaling components of native VLDL are its triglycerides, whose activity is enhanced by lipoprotein" lipase. Generation of peroxisome proliferator-activated receptor delta 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.