Journal
CARDIOVASCULAR RESEARCH
Volume 98, Issue 3, Pages 479-487Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvt073
Keywords
Fatty acids; Lipoproteins; Macrophages; Metabolism; Oxidized lipids
Categories
Funding
- Deutsche Forschungsgemeinschaft [BR999]
- Translational Research Innovation Pharma (TRIP)
- LOEWE-Schwerpunkt: Anwendungsorientierte Arzneimittelforschung
Ask authors/readers for more resources
Transcriptional regulation through peroxisome proliferator-activated receptor (PPAR) is critical for an altered lipid metabolism during monocyte to macrophage differentiation. Here, we investigated how 5-aminoimidazole-4-carboxamide riboside (AICAR), an activator of AMP-dependent protein kinase (AMPK), affects PPAR during monocyte differentiation. During the differentiation of THP-1 monocytic cells or primary human monocytes to macrophages, we observed that AICAR inhibited the expression of PPAR target genes, such as fatty acid-binding protein 4 or CD36. This effect was independent of AICAR conversion to AICAR ribotide and AMPK activation. While AICAR increased PPAR mRNA expression that paralleled differentiation, it inhibited PPAR protein synthesis without affecting PPAR protein stability. Monocytes differentiated to macrophages in the presence of AICAR revealed an attenuated uptake of oxidized low-density lipoprotein (oxLDL) and reduced oxLDL-triggered c-Jun N-terminal kinase (JNK) activation. JNK and endoplasmic reticulum stress responses to the saturated fatty acid palmitate were attenuated as well, an effect mimicked by the knockdown of PPAR. Although PPAR has been reported to support alternative macrophage activation, AICAR did not inhibit interleukin-4-induced gene expression in differentiating monocytes. Inhibition of PPAR-dependent gene expression during monocyte differentiation may contribute to an AICAR-elicited macrophage phenotype characterized by reduced inflammatory responses to modified lipoproteins and saturated fatty acids.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available