scholarly journals Peroxisome Proliferator-Activated Receptors and Liver X Receptors in Atherosclerosis and Immunity

2006 ◽  
Vol 136 (3) ◽  
pp. 690-694 ◽  
Author(s):  
Grant D. Barish
Keyword(s):  
Peroxisome Proliferator ◽  
Liver X Receptors ◽  
Peroxisome Proliferator Activated Receptors ◽  
X Receptors

scholarly journals Lysosome-Dependent LXR and PPARδ Activation Upon Efferocytosis in Human Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana Carolina Mota ◽  
Monica Dominguez ◽  
Andreas Weigert ◽  
Ryan G. Snodgrass ◽  
Dmitry Namgaladze ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Liver X Receptors ◽  
Human Macrophages ◽  
Sterol Regulatory Element ◽  
Peroxisome Proliferator Activated Receptors ◽  
X Receptors

Efferocytosis is critical for tissue homeostasis, as its deregulation is associated with several autoimmune pathologies. While engulfing apoptotic cells, phagocytes activate transcription factors, such as peroxisome proliferator-activated receptors (PPAR) or liver X receptors (LXR) that orchestrate metabolic, phagocytic, and inflammatory responses towards the ingested material. Coordination of these transcription factors in efferocytotic human macrophages is not fully understood. In this study, we evaluated the transcriptional profile of macrophages following the uptake of apoptotic Jurkat T cells using RNA-seq analysis. Results indicated upregulation of PPAR and LXR pathways but downregulation of sterol regulatory element-binding proteins (SREBP) target genes. Pharmacological inhibition and RNA interference pointed to LXR and PPARδ as relevant transcriptional regulators, while PPARγ did not substantially contribute to gene regulation. Mechanistically, lysosomal digestion and lysosomal acid lipase (LIPA) were required for PPAR and LXR activation, while PPARδ activation also demanded an active lysosomal phospholipase A2 (PLA2G15). Pharmacological interference with LXR signaling attenuated ABCA1-dependent cholesterol efflux from efferocytotic macrophages, but suppression of inflammatory responses following efferocytosis occurred independently of LXR and PPARδ. These data provide mechanistic details on LXR and PPARδ activation in efferocytotic human macrophages.

scholarly journals Intestinal and Hepatic Cholesterol Carriers in Diabetic Psammomys obesus

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 958-970 ◽  
Author(s):  
Emile Levy ◽  
Geneviève Lalonde ◽  
Edgard Delvin ◽  
Mounib Elchebly ◽  
Louis P. Précourt ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
The Other ◽  
Peroxisome Proliferator ◽  
Type I ◽  
Liver X Receptors ◽  
Psammomys Obesus ◽  
Annexin 2 ◽  
Peroxisome Proliferator Activated Receptors ◽  
Niemann Pick ◽  
X Receptors

Insulin resistance and type 2 diabetes (T2D) are characterized by hyperlipidemia. The aim of the present study was to elucidate whether T2D contributes to abnormal cholesterol (CHOL) homeostasis. Experiments were carried out in the small intestine and liver of Psammomys obesus, a model of nutritionally induced T2D. Our results show that diabetic animals exhibited a lower intestinal CHOL uptake, which was associated with a decrease in 1) the gene and protein expression of Niemann-Pick C1 like 1 that plays a pivotal role in CHOL incorporation in the enterocytes; and 2) mRNA of ATP-binding cassette transporters (ABC)A1 that mediates CHOL efflux from intestinal cells to apolipoprotein A-I and high-density lipoprotein. No changes were observed in the other intestinal transporters scavenger receptor-class B type I (SR-BI) and annexin 2. On the other hand, in diabetic animals, a significant mRNA decrease was noticed in intestinal ABCG5 and ABCG8 responsible for the secretion of absorbed CHOL back into the lumen. Furthermore, jejunal PCSK9 protein was diminished and low-density lipoprotein receptor was raised, along with a significant down-regulation in jejunal 3-hydroxy-3-methylglutaryl-coenzyme A reductase in P. obesus with T2D. Finally, among the transcription factors tested, only an increase in liver X receptors α and a decrease in peroxisome proliferator-activated receptors δ/β mRNAs were detected in the intestine. In the liver, there was 1) an augmentation in the protein mass of Niemann-Pick C1 like 1, SR-BI, and annexin 2; 2) an up-regulation of SR-BI mRNA; 3) a fall in ABCG8 protein content as well as in ABCG5 and ABCA1 mRNA; and 4) an augmentation in liver X receptors α and peroxisome proliferator-activated receptors β/δ mRNA, together with a drop in sterol regulatory element binding protein-2 protein. Our findings show that the development in P. obesus with T2D modifies the whole intraenterocyte and hepatocyte machinery responsible for CHOL homeostasis.

Transcriptional regulation of macrophage cholesterol trafficking by PPARα and LXR

2006 ◽  
Vol 34 (6) ◽  
pp. 1128-1131 ◽  
Author(s):  
G. Chinetti ◽  
J.C. Fruchart ◽  
B. Staels
Keyword(s):  
Transcription Factors ◽  
Peroxisome Proliferator ◽  
Liver X Receptors ◽  
Cholesterol Trafficking ◽  
Peroxisome Proliferator Activated Receptors ◽  
Atherosclerosis Development ◽  
X Receptors ◽  
And Function ◽  
Atherosclerosis Research

PPARs (peroxisome-proliferator-activated receptors) and LXRs (liver X receptors) are ligand-activated transcription factors that control lipid and glucose metabolism, as well as the inflammatory response. Since the macrophage plays an important role in host defence and immuno-inflammatory pathologies, particular attention has been paid to the role of PPARs and LXRs in the control of macrophage gene expression and function. Altered macrophage functions contribute to the pathogenesis of many infectious, immunological and inflammatory disease processes, including atherosclerosis. Research over the last few years has revealed important roles for PPARs and LXRs in macrophage inflammation and cholesterol homoeostasis with consequences in atherosclerosis development. This review will discuss the role of these transcription factors in the control of cholesterol trafficking in macrophages.

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