Rational application of macrophage-specific LXR agonists avoids the pitfalls of SREBP-induced lipogenesis

Magida, Jason A.; Evans, Ronald M.

doi:10.1073/pnas.1805128115

Cited by 10 publications

(7 citation statements)

References 10 publications

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“…We cannot exclude the possibility that the timely differences between the tissue-specific LXR deletion and the LXR agonist injected mice are due to unique pathways. Indeed, previous studies have demonstrated that gene expression response to synthetic LXR agonists could be different from the response to endogenous cholesterol-derived LXR ligands (Magida and Evans, 2018;Muse et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

Liver X Receptors Protect Dorsal Root Ganglia from Obesity-Induced Endoplasmic Reticulum Stress and Mechanical Allodynia

et al. 2018

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Section: Resultsmentioning

confidence: 99%

Liver X Receptors Protect Dorsal Root Ganglia from Obesity-Induced Endoplasmic Reticulum Stress and Mechanical Allodynia

et al. 2018

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“…LXR is a ligand-activated transcription factor, presented as two isoforms, LXRα and LXRβ, which are differentially expressed in different organs [ 127 ]. LXR is able to bind to cholesterol derivatives and intermediate products of its biosynthesis, as well as polyunsaturated fatty acids and some other compounds [ 128 , 129 , 130 , 131 ]. In this case oxysterols act as agonists, while, for example, arachidonic acid, to the contrary, exhibits antagonistic properties [ 129 , 130 , 131 ].…”

Section: Disorders Of Lipid Metabolism In the Development And Progression Of Nafldmentioning

confidence: 99%

Lipid Metabolism Disorders in the Comorbid Course of Nonalcoholic Fatty Liver Disease and Chronic Obstructive Pulmonary Disease

Kotlyarov

Bulgakov

2021

Cells

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Non-alcoholic fatty liver disease (NAFLD) is currently among the most common liver diseases. Unfavorable data on the epidemiology of metabolic syndrome and obesity have increased the attention of clinicians and researchers to the problem of NAFLD. The research results allow us to emphasize the systemicity and multifactoriality of the pathogenesis of liver parenchyma lesion. At the same time, many aspects of its classification, etiology, and pathogenesis remain controversial. Local and systemic metabolic disorders are also a part of the pathogenesis of chronic obstructive pulmonary disease and can influence its course. The present article analyzes the metabolic pathways mediating the links of impaired lipid metabolism in NAFLD and chronic obstructive pulmonary disease (COPD). Free fatty acids, cholesterol, and ceramides are involved in key metabolic and inflammatory pathways underlying the pathogenesis of both diseases. Moreover, inflammation and lipid metabolism demonstrate close links in the comorbid course of NAFLD and COPD.

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“…Only Abcg1 levels were decreased in PirB MΦKO macrophages ( Figure 5E ). As Abcg1 is positively regulated by LXRα/β signaling, we treated the acLDL-exposed PirB flox and PirB MΦKO macrophages with the LXRα/β agonists GW3965 or T0901317 ( Magida and Evans, 2018 ). Notably, both LXRα/β agonists induced Abcg1 upregulation in PirB flox but not PirB MΦKO macrophages ( Figure 5F ).…”

Section: Resultsmentioning

confidence: 99%

Macrophage Paired Immunoglobulin-Like Receptor B Deficiency Promotes Peripheral Atherosclerosis in Apolipoprotein E–Deficient Mice

Liang

Zhou

Cao

et al. 2022

Front. Cell Dev. Biol.

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Background: Peripheral atherosclerotic disease (PAD) is the narrowing or blockage of arteries that supply blood to the lower limbs. Given its complex nature, bioinformatics can help identify crucial genes involved in the progression of peripheral atherosclerosis.Materials and Methods: Raw human gene expression data for 462 PAD arterial plaque and 23 normal arterial samples were obtained from the GEO database. The data was analyzed using an integrated, multi-layer approach involving differentially-expressed gene analysis, KEGG pathway analysis, GO term enrichment analysis, weighted gene correlation network analysis, and protein-protein interaction analysis. The monocyte/macrophage-expressed leukocyte immunoglobulin-like receptor B2 (LILRB2) was strongly associated with the human PAD phenotype. To explore the role of the murine LILRB2 homologue PirB in vivo, we created a myeloid-specific PirB-knockout Apoe−/− murine model of PAD (PirBMΦKO) to analyze femoral atherosclerotic burden, plaque features of vulnerability, and monocyte recruitment to femoral atherosclerotic lesions. The phenotypes of PirBMΦKO macrophages under various stimuli were also investigated in vitro.Results:PirBMΦKO mice displayed increased femoral atherogenesis, a more vulnerable plaque phenotype, and enhanced monocyte recruitment into lesions. PirBMΦKO macrophages showed enhanced pro-inflammatory responses and a shift toward M1 over M2 polarization under interferon-γ and oxidized LDL exposure. PirBMΦKO macrophages also displayed enhanced efferocytosis and reduced lipid efflux under lipid exposure.Conclusion: Macrophage PirB reduces peripheral atherosclerotic burden, stabilizes peripheral plaque composition, and suppresses macrophage accumulation in peripheral lesions. Macrophage PirB inhibits pro-inflammatory activation, inhibits efferocytosis, and promotes lipid efflux, characteristics critical to suppressing peripheral atherogenesis.

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Rational application of macrophage-specific LXR agonists avoids the pitfalls of SREBP-induced lipogenesis

Cited by 10 publications

References 10 publications

Liver X Receptors Protect Dorsal Root Ganglia from Obesity-Induced Endoplasmic Reticulum Stress and Mechanical Allodynia

Liver X Receptors Protect Dorsal Root Ganglia from Obesity-Induced Endoplasmic Reticulum Stress and Mechanical Allodynia

Lipid Metabolism Disorders in the Comorbid Course of Nonalcoholic Fatty Liver Disease and Chronic Obstructive Pulmonary Disease

Macrophage Paired Immunoglobulin-Like Receptor B Deficiency Promotes Peripheral Atherosclerosis in Apolipoprotein E–Deficient Mice

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