Emerging roles of SIRT1 in fatty liver diseases

Ding, Ren-Bo; Bao, Jiaolin; Deng, Chu‐Xia

doi:10.7150/ijbs.19370

Cited by 278 publications

(232 citation statements)

References 173 publications

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“…It has been well‐documented by both pharmacological and genetic studies that sirtuin 1 (SIRT1), a class III nicotinamide adenine dinucleotide (NAD + )‐dependent histone/protein deacetylase, is a crucial regulator of liver fat metabolism that prevents and improves NAFLD features and many other obesity‐related diseases . SIRT1 works as a main energy sensor and regulates homeostatic transcriptional responses .…”

mentioning

confidence: 99%

“…It has been well-documented by both pharmacological and genetic studies that sirtuin 1 (SIRT1), a class III nicotinamide adenine dinucleotide (NAD + )-dependent histone/protein deacetylase, is a crucial regulator of liver fat metabolism that prevents and improves NAFLD features and many other obesity-related diseases. (5) SIRT1 works as a main energy sensor and regulates homeostatic transcriptional responses. (6) SIRT1 deacetylates liver kinase B1 (LKB1), which in turn affects the adenosine monophosphate-activated protein kinase (AMPK) phosphorylation on threonine (Thr) 172, an event that is required for its activation (7) and further action on cellular energy state, mitochondrial function, and lipid metabolism.…”

mentioning

confidence: 99%

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Pirfenidone Is an Agonistic Ligand for PPARα and Improves NASH by Activation of SIRT1/LKB1/pAMPK

Sandoval-Rodríguez¹,

Monroy-Ramírez²,

Meza-Ríos

et al. 2020

Hepatol Commun

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Nonalcoholic steatohepatitis (NASH) is recognized by hepatic lipid accumulation, inflammation, and fibrosis. No studies have evaluated the prolonged‐release pirfenidone (PR‐PFD) properties on NASH features. The aim of this study is to evaluate how PR‐PFD performs on metabolic functions, and provide insight on a mouse model of human NASH. Male C57BL/6J mice were fed with either normo diet or high‐fat/carbohydrate diet for 16 weeks and a subgroup also fed with PR‐PFD (300 mg/kg/day). An insulin tolerance test was performed at the end of treatment. Histological analysis, determination of serum hormones, adipocytokines measurement, and evaluation of proteins by western blot was performed. Molecular docking, in silico site‐directed mutagenesis, and in vitro experiments using HepG2 cultured cells were performed to validate PR‐PFD binding to peroxisome proliferator–activated receptor alpha (PPAR‐α), activation of PPAR‐α promoter, and sirtuin 1 (SIRT1) protein expression. Compared with the high‐fat group, the PR‐PFD‐treated mice displayed less weight gain, cholesterol, very low density lipoprotein and triglycerides, and showed a significant reduction of hepatic macrosteatosis, inflammation, hepatocyte ballooning, fibrosis, epididymal fat, and total adiposity. PR‐PFD restored levels of insulin, glucagon, adiponectin, and resistin along with improved insulin resistance. Noteworthy, SIRT1–liver kinase B1–phospho‐5′ adenosine monophosphate–activated protein kinase signaling and the PPAR‐α/carnitine O‐palmitoyltransferase 1/acyl‐CoA oxidase 1 pathway were clearly induced in high fat + PR‐PFD mice. In HepG2 cells incubated with palmitate, PR‐PFD induced activation and nuclear translocation of both PPARα and SIRT1, which correlated with increased SIRT1 phosphorylated in serine 47, suggesting a positive feedback loop between the two proteins. These results were confirmed with both synthetic PPAR‐α and SIRT1 activators and inhibitors. Finally, we found that PR‐PFD is a true agonist/ligand for PPAR‐α. Conclusions: PR‐PFD provided an anti‐steatogenic effect and protection for inflammation and fibrosis.

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confidence: 99%

mentioning

confidence: 99%

Pirfenidone Is an Agonistic Ligand for PPARα and Improves NASH by Activation of SIRT1/LKB1/pAMPK

Sandoval-Rodríguez¹,

Monroy-Ramírez²,

Meza-Ríos

et al. 2020

Hepatol Commun

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“…Mammals have 7 sirtuin family members that are divided into 4 classes: class I, including SIRT1, SIRT2, and SIRT3; class II, SIRT4; class III, SIRT5; and class IV, SIRT6 and SIRT7 (12,13). Among them, SIRT1 has been shown to be the essential molecule responsible for hepatic lipid metabolism and inflammation via deacetylating some transcriptional regulators (14)(15)(16). SIRT3-deficient animals display striking mitochondrial protein hyperacetylation, which suggests that SIRT3 is a major mitochondrial deacetylase (17).…”

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confidence: 99%

SIRT7 functions in redox homeostasis and cytoskeletal organization during oocyte maturation

Gao

et al. 2018

FASEB j.

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SIRT7, a member of the sirtuin family, with coenzyme NAD catalyzes protein deacetylation and has been implicated in multiple biologic processes; however, its function in mammalian oocytes remains to be explored. Here, we report disrupted meiotic maturation upon specific knockdown of SIRT7 in mouse oocytes. In particular, disorganized spindle/chromosomes and the loss of the cortical actin cap are readily observed in SIRT7-depleted oocytes, generating aneuploid eggs. Furthermore, we found that SIRT7 depletion markedly elevated reactive oxygen species levels in oocytes, thereby compromising the developmental competence of early embryos. Of note, SIRT7 protein level is significantly decreased in oocytes from obese mice, and the forced expression of exogenous SIRT7 ameliorates maternal obesity-associated meiotic defects and oxidative stress in oocytes. In summary, our data suggest that SIRT7 is an essential factor in the determination of oocyte quality and may mediate the effects of obesity on female reproduction.-Gao, M., Li, X., He, Y., Han, L., Qiu, D., Ling, L., Liu, H., Liu, J., Gu, L. SIRT7 functions in redox homeostasis and cytoskeletal organization during oocyte maturation.

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“…AMPK is a key cellular energy sensor and regulator and has been shown to be decreased in metabolic syndrome . SIRT1 is an important downstream molecule of the AMPK pathway and is a regulator of gluconeogenesis and lipid metabolism . We are first to report that l ‐Met‐S increases hepatic p‐AMPK/AMPK ratio and SIRT1 in HFD + low dose STZ‐induced diabetic animals, similar to the antidiabetic drug metformin.…”

Section: Discussionmentioning

confidence: 63%

Dietary Supplementation of Methyl Donor l‐Methionine Alters Epigenetic Modification in Type 2 Diabetes

Navik

Sheth

Kabeer

et al. 2019

Molecular Nutrition Food Res

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Scope The aim of the current study is to evaluate whether l‐methionine supplementation (l‐Met‐S) improves type 2 diabetes‐induced alterations in glucose and lipid metabolism by modulating one‐carbon metabolism and methylation status. Methods and Results Diabetes is induced in male Sprague–Dawley rats using high‐fat diet and low dose streptozotocin. At the end of study, various biochemical parameters, immunoblotting, qRT‐PCR and ChIP‐qPCR are performed. The first evidence that l‐Met‐S activates p‐AMPK and SIRT1, very similar to “metformin,” is provided. l‐Met‐S improves the altered key one‐carbon metabolites in diabetic rats by modulating methionine adenosyl transferase 1A and cystathione β synthase expression. qRT‐PCR shows that l‐Met‐S alleviates diabetes‐induced increase in Forkhead transcription factor 1 expression and thereby regulating genes involved in glucose (G6pc, Pdk4, Pklr) and lipid metabolism (Fasn). Interestingly, l‐Met‐S inhibits the increased expression of DNMT1 and also prevents methylation of histone H3K36me2 under diabetic condition. ChIP assay shows that persistent increase in abundance of histone H3K36me2 on the promoter region of FOXO1 in diabetic rats and it is recovered by l‐Met‐S. Conclusion The first evidence that dietary supplementation of l‐Met prevents diabetes‐induced epigenetic alterations and regulating methionine levels can be therapeutically exploited for the treatment of metabolic diseases is provided.

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Emerging roles of SIRT1 in fatty liver diseases

Cited by 278 publications

References 173 publications

Pirfenidone Is an Agonistic Ligand for PPARα and Improves NASH by Activation of SIRT1/LKB1/pAMPK

Pirfenidone Is an Agonistic Ligand for PPARα and Improves NASH by Activation of SIRT1/LKB1/pAMPK

SIRT7 functions in redox homeostasis and cytoskeletal organization during oocyte maturation

Dietary Supplementation of Methyl Donor l‐Methionine Alters Epigenetic Modification in Type 2 Diabetes

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