Inflammation Triggers Liver X Receptor-Dependent Lipogenesis

Liebergall, Sophie R.; Angdisen, Jerry; Chan, Shun Hang; Chang, Yuan‐Jen; Osborne, Timothy F.; Koeppel, Alexander F.; Turner, Stephen D.; Schulman, Ira G.

doi:10.1128/mcb.00364-19

Cited by 25 publications

(25 citation statements)

References 76 publications

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“…10e ). While this inhibits their cholesterol synthesizing machinery by feedback control 37 , the pro-inflammatory milieu promotes cholesterol synthesis 38 . Indeed, we observed upregulated transcripts of sterol synthesizing enzymes apart from Dhcr24 mRNA, encoding the last enzyme of cholesterol biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis

et al. 2020

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The repair of inflamed, demyelinated lesions as in multiple sclerosis necessitates the clearance of cholesterol-rich myelin debris by microglia/macrophages and the switch from a pro-inflammatory to an anti-inflammatory lesion environment. Subsequently, oligodendrocytes increase cholesterol levels as a prerequisite for synthesizing new myelin membranes. We hypothesized that lesion resolution is regulated by the fate of cholesterol from damaged myelin combined with oligodendroglial sterol synthesis. By integrating expression profiling, genetics, and comprehensive phenotyping, we found that paradoxically sterol synthesis in myelin-phagocytosing microglia/macrophages determines repair of acutely demyelinated lesions. Rather than producing cholesterol, microglia/macrophages synthesized desmosterol, the immediate cholesterol precursor. Desmosterol activated LXR-signaling to resolve inflammation, creating a permissive environment for oligodendrocyte differentiation. Moreover, LXR-target gene products facilitated the efflux of lipid/cholesterol from lipid-laden microglia/macrophages to support remyelination by oligodendrocytes. Consequently, pharmacological stimulation of sterol synthesis boosted repair of demyelinated lesions, suggesting novel therapeutic strategies for myelin repair in multiple sclerosis.

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Section: Discussionmentioning

confidence: 99%

Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis

et al. 2020

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“…Down-regulation of SREBP expression is thus a likely explanation for the reduction in both fat accumulation in the liver and cholesterol and triglycerides levels in serum observed in the HFD+Vinegar_Bc mice. Additionally, activation of LXR has also been described to have anti-inflammatory effects in steatosis [55,56]. Therefore, the reduction in LXR expression could reflect the effect of vinegar and B. coagulans on systemic inflammation.…”

Section: Discussionmentioning

confidence: 99%

A Combination of Apple Vinegar Drink with Bacillus coagulans Ameliorates High Fat Diet-Induced Body Weight Gain, Insulin Resistance and Hepatic Steatosis

Urtasun

Díaz-Gómez²,

Araña

et al. 2020

Nutrients

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Obesity is a worldwide epidemic characterized by excessive fat accumulation, associated with multiple comorbidities and complications. Emerging evidence points to gut microbiome as a driving force in the pathogenesis of obesity. Vinegar intake, a traditional remedy source of exogenous acetate, has been shown to improve glycemic control and to have anti-obesity effects. New functional foods may be developed by supplementing traditional food with probiotics. B. coagulans is a suitable choice because of its resistance to high temperatures. To analyze the possible synergic effect of Vinegar and B. coagulans against the metabolic alterations induced by a high fat diet (HFD), we fed twelve-week-old C57BL/6 mice with HFD for 5 weeks after 2 weeks of acclimation on a normal diet. Then, food intake, body weight, blood biochemical parameters, histology and liver inflammatory markers were analyzed. Although vinegar drink, either alone or supplemented with B. coagulans, reduced food intake, attenuated body weight gain and enhanced glucose tolerance, only the supplemented drink improved the lipid serum profile and prevented hepatic HFD-induced overexpression of CD36, IL-1β, IL-6, LXR and SREBP, thus reducing lipid deposition in the liver. The beneficial properties of the B. coagulans-supplemented vinegar appear to be mediated by a reduction in insulin and leptin circulating levels.

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“…The modulation of lipid metabolism via these transcription factors is important for short term immune cell activation as well as long-term trained innate immunity 58,[71][72][73][74] . However, loss of function experiments indicated that LXRs and SREBPs were not required for the antiinflammatory effects of 3'SL on LPS treated macrophages.…”

Section: Discussionmentioning

confidence: 99%

The Human Milk Oligosaccharide 3’Sialyllactose Promotes Inflammation Resolution and Reduces Atherosclerosis Development in Mice

Pessentheiner¹,

Spann²,

Autran³

et al. 2021

Preprint

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SUMMARYMacrophages contribute to the induction and resolution of inflammation and play a central role in the chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3’sialyllactose (3’SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium. Transcriptome analysis in macrophages revealed that 3’SL attenuates a selected set of inflammatory gene expression and promotes activity of LXR and SREBP. These acute anti-inflammatory effects of 3’SL were associated with reduced histone H3K27 acetylation at a subset of LPS-inducible enhancers distinguished by preferential enrichment for CTCF, IRF2, BCL6, and other transcription factor recognition motifs. In a murine atherosclerosis model, both subcutaneous and oral administration of 3’SL significantly reduced atherosclerosis development and the associated inflammation. This study provides evidence that 3’SL attenuates inflammation by a transcriptional mechanism to reduce atherosclerosis development in the context of cardiovascular disease.

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Inflammation Triggers Liver X Receptor-Dependent Lipogenesis

Cited by 25 publications

References 76 publications

Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis

Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis

A Combination of Apple Vinegar Drink with Bacillus coagulans Ameliorates High Fat Diet-Induced Body Weight Gain, Insulin Resistance and Hepatic Steatosis

The Human Milk Oligosaccharide 3’Sialyllactose Promotes Inflammation Resolution and Reduces Atherosclerosis Development in Mice

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