Metabolic Regulation of Macrophages by SIRT1 Determines Activation During Cholestatic Liver Disease in Mice

Isaacs‐Ten, Anna; Moreno‐Gonzalez, Mar; Bone, Caitlin; Märtens, Andre; Bernuzzi, Federico; Ludwig, Tobias; Hellmich, Charlotte; Hiller, Karsten; Rushworth, Stuart A.; Beraza, Naiara

doi:10.1016/j.jcmgh.2021.12.010

Cited by 16 publications

(12 citation statements)

References 73 publications

(208 reference statements)

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“…SIRT1 contributes to the function and biogenesis of mitochondria [ 33 ]. Of note, Samadi et al [ 34 ] described that SIRT1 expression is suppressed in a diabetic dry eye model.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Potential of Resveratrol in Dry Eye Disease by Restoring Mitochondrial Function

Chen

Zhang

Zheng

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background and Significance. Dry eye disease (DED) is a prevalent optic surface illness with a high incidence worldwide that is caused by a variety of factors, including mitochondrial dysfunction. Resveratrol has been confirmed to protect the eye surface in DED, and as an antioxidant, resveratrol can maintain mitochondrial function. Therefore, we investigated whether resveratrol can improve DED by restoring mitochondrial function. Methods. The mitochondrial dysfunction of HCE-2 human corneal epithelial cells was induced by high osmotic pressure exposure and treated with resveratrol (50 μM). Western blotting was used to detect the expression of the antioxidant proteins SOD2, GPx, and SIRT1, and flow cytometry was used to detect cell apoptosis and ROS production. The DED mouse model was induced by 0.2% benzalkonium chloride (BAC) and treated with resveratrol. The tear yield was measured by the phenol cotton thread test, the density of cup cells in the conjunctiva was measured by periodic acid-Schiff (PAS) staining, and the expression levels of SIRT1, GPx, and SOD2 in lacrimal glands were detected by Western blotting. Results. In hypertonic conditions, the apoptosis of HCE-2 cells increased, the expression of the antioxidant proteins SOD2 and GPx decreased, ROS production increased, and the expression of SIRT1 protein, an essential regulator of mitochondrial function, was downregulated. Treatment with resveratrol reversed the mitochondrial dysfunction mediated by high osmotic pressure. In the DED mouse model, resveratrol treatment promoted tear production and goblet cell number in DED mice, decreased corneal fluorescein staining, upregulated SIRT1 expression, and induced SOD2 and GPx expression in DED mice. Conclusion. Resveratrol alleviates mitochondrial dysfunction by promoting SIRT1 expression, thus reducing ocular surface injury in mice with dry eye. This study suggests a new path against DED.

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“…SIRT1 contributes to the function and biogenesis of mitochondria [ 33 ]. Of note, Samadi et al [ 34 ] described that SIRT1 expression is suppressed in a diabetic dry eye model.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Potential of Resveratrol in Dry Eye Disease by Restoring Mitochondrial Function

Chen

Zhang

Zheng

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Another study demonstrated that hepatic stellate cells (HSC)specific SIRT1 knockout mice were more susceptible to long-term chronic-plus-multiple binges of ethanol-induced liver fibrosis (160). In contrast, Isaacs-Ten et al found that SIRT1 promotes increased liver inflammation and injuries post-LPS/GalN and bile duct ligation, associated with elevated activation of inflammasomes in macrophages (163). These contradictory findings suggest that SIRT1 might be a promising target for therapeutic intervention in hepatic inflammatory diseases, but further investigation is required.…”

Section: Livermentioning

confidence: 99%

“…In contrast, Isaacs-Ten et al. found that SIRT1 promotes increased liver inflammation and injuries post-LPS/GalN and bile duct ligation, associated with elevated activation of inflammasomes in macrophages ( 163 ). These contradictory findings suggest that SIRT1 might be a promising target for therapeutic intervention in hepatic inflammatory diseases, but further investigation is required.…”

Section: Sirt1 In the Regulation Of Inflammationmentioning

confidence: 99%

Regulation of SIRT1 and Its Roles in Inflammation

et al. 2022

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The silent information regulator sirtuin 1 (SIRT1) protein, a highly conserved NAD+-dependent deacetylase belonging to the sirtuin family, is a post-translational regulator that plays a role in modulating inflammation. SIRT1 affects multiple biological processes by deacetylating a variety of proteins including histones and non-histone proteins. Recent studies have revealed intimate links between SIRT1 and inflammation, while alterations to SIRT1 expression and activity have been linked to inflammatory diseases. In this review, we summarize the mechanisms that regulate SIRT1 expression, including upstream activators and suppressors that operate on the transcriptional and post-transcriptional levels. We also summarize factors that influence SIRT1 activity including the NAD+/NADH ratio, SIRT1 binding partners, and post-translational modifications. Furthermore, we underscore the role of SIRT1 in the development of inflammation by commenting on the proteins that are targeted for deacetylation by SIRT1. Finally, we highlight the potential for SIRT1-based therapeutics for inflammatory diseases.

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“…In addition, SIRT1 regulates the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor to modulate airway inflammation [ 48 ]. In contrast, SIRT1, through activating mTOR, contributes to hepatic inflammation, inflammasome activation, and liver injury [ 49 ]. Future studies will provide insights into the SIRT1 crosstalks to mTOR pathway to alleviate discrepancies in different experimental settings.…”

Section: Overview Of Sirtsmentioning

confidence: 99%

“…A growing body of literature suggests an essential role for SIRT1 in regulating immunometabolic pathways to impact the immune and inflammatory responses [ 49 , 50 ]. Upon TLR4 stimulation, SIRT1, coupling to a cofactor NAD + , regulates epigenetic reprogramming for the coordinated bioenergetic and inflammatory responses [ 51 , 52 ].…”

Section: Overview Of Sirtsmentioning

confidence: 99%

Sirtuin 1 in Host Defense during Infection

Kim

Silwal

2022

Cells

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Sirtuins (SIRTs) are members of the class III histone deacetylase family and epigenetically control multiple target genes to modulate diverse biological responses in cells. Among the SIRTs, SIRT1 is the most well-studied, with a role in the modulation of immune and inflammatory responses following infection. The functions of SIRT1 include orchestrating immune, inflammatory, metabolic, and autophagic responses, all of which are required in establishing and controlling host defenses during infection. In this review, we summarize recent information on the roles of SIRT1 and its regulatory mechanisms during bacterial, viral, and parasitic infections. We also discuss several SIRT1 modulators, as potential antimicrobial treatments. Understanding the function of SIRT1 in balancing immune homeostasis will contribute to the development of new therapeutics for the treatment of infection and inflammatory disease.

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Metabolic Regulation of Macrophages by SIRT1 Determines Activation During Cholestatic Liver Disease in Mice

Abstract: Here, we describe that the SIRT1/mTOR axis regulates metabolic rewiring, inflammasome activation, and autophagy in macrophages, in which SIRT1 overexpression actively contributes to aggravate cholestatic liver disease progression in mice.

Cited by 16 publications

References 73 publications

Ameliorative Potential of Resveratrol in Dry Eye Disease by Restoring Mitochondrial Function

Ameliorative Potential of Resveratrol in Dry Eye Disease by Restoring Mitochondrial Function

Regulation of SIRT1 and Its Roles in Inflammation

Sirtuin 1 in Host Defense during Infection

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