A Potential Treatment of Non-Alcoholic Fatty Liver Disease with SIRT1 Activators

Çolak, Yaşar; Yeşıl, Atakan; Mutlu, Hasan; Çaklılı, Özge Telci; Ulasoglu, Celal; Şenateş, Ebubekir; Takır, Mümtaz; Köstek, Osman; Yılmaz, Yusuf; Enç, Feruze Yılmaz; Taşan, Güralp; Tuncer, İlyas

doi:10.15403/jgld.2014.1121.233.yck

Cited by 85 publications

(64 citation statements)

References 109 publications

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“…Sirtuin 1 (SIRT1) is reported to have therapeutic potential in NAFLD and play a key role in insulin sensitivity [14] . SIRT1 regulates the expression of peroxisome proliferators activated receptor (PPAR)-α, a key factor in the regulation of lipid metabolism [15,16] .…”

Section: Resultsmentioning

confidence: 99%

Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats

Qiu¹,

Gao²,

Xiang³

et al. 2015

WJG

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Section: Resultsmentioning

confidence: 99%

Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats

Qiu¹,

Gao²,

Xiang³

et al. 2015

WJG

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“…Remarkably, the molecular mechanisms of the action of taurine in correction of NAFLD was reported in the study of Banks et al [43], who explained that taurine increases the expression of SIRT1 in the liver which further stimulates the antioxidant capacity, by SOD induction and lowering the proinflammatory signals, TNF-α and interleukin 6 (IL-6). Moreover, taurine was reported to induce overexpression of SIRT1 in mice which provided protection against HFD induced hepatic steatosis through upregulation of fatty acid oxidation and downregulation of lipogenesis [15]. …”

Section: Discussionmentioning

confidence: 99%

“…Sirtuins type 1 (SIRT1), an important histone deacetylase, is a potential molecule and main determinant of whole body homeostasis in mammals by regulating many transcriptional regulators in metabolic tissues such as liver, skeletal muscle and adipose tissues [15]. SIRT1 and its activators play a key role in lipid and glucose homeostasis and insulin sensitivity via regulating mitochondrial biogenesis and β-oxidation, and improving anti-inflammatory activities.…”

Section: Introductionmentioning

confidence: 99%

“…SIRT1 and its activators play a key role in lipid and glucose homeostasis and insulin sensitivity via regulating mitochondrial biogenesis and β-oxidation, and improving anti-inflammatory activities. Previous studies indicated that the activation of SIRT1 in the liver protects against high-fat diet (HFD)-induced metabolic damage [15, 16], and that the regulation of hepatic lipid metabolism is postulated by SIRT1 deacetylation of sterol regulatory element-binding protein (SREBP)-1c, thus decreasing its expression [17, 18]. Despite the high prevalence of NAFLD, an approved standardized treatment is still lacking, contributing to a serious challenge to health care systems.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Role of SIRT1/ FGF-21 in Taurine Protection Against Cafeteria Diet-Induced Steatohepatitis in Rats

Elwahab

Ramadan

Schaalan

et al. 2017

Cell Physiol Biochem

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Background: Non-alcoholic fatty liver disease (NAFLD) is one of the alarmingly rising clinical problems in the 21^st century with no effective drug treatment until now. Taurine is an essential amino acid in humans that proved efficacy as a non-pharmacological therapy in a plethora of diseases; however, its impact on NAFLD remains elusive. The aim of the current study is to evaluate the protective mechanism of taurine in experimental steatohepatitis induced by junk food given as cafeteria-diet (CAF-D) in male albino rats. Methods: Forty adult male albino rats of local strain between 8-10 weeks old, weighing 150 ± 20 g, were divided into four equal groups: Group I (control group), Group II (Taurine group), Group III (CAF-D for 12 weeks) and Group IV (CAF-D +Taurine). CAF-D was given in addition to the standard chow for 12 weeks, where each rat was given one piece of beef burger fried in 15 g of sunflower oil, one teaspoonful of mayonnaise, and one piece of petit pan bread, weighing 60g/ piece. In the serum, liver function tests; ALT, AST, ALP, GGT and the lipid profile; TG, TC, HDL-C added to reduced glutathione (GSH) were assessed colorimetrically, while fibroblast growth factor (FGF)-21, adiponectin & interleukin (IL)-6 via ELISA. The same technique was used for the assays of the hepatic levels of FGF-21, silent information regulator (SIRT1), malondialdehyde (MDA),IL-10, tumor necrosis factor-α (TNF-α) as well as the apoptotic markers; caspase-3 and B-cell lymphoma (Bcl-2). Results: The cafeteria-diet induced steatohepatitis was reflected by significantly increased body and liver weight gain, elevation of liver enzymes; ALT, AST, ALP and GGT added to the dyslipidemic panel, presented as increased TC, TG, LDL-C and decreased HDL-C levels. The steatosis-induced inflammatory milieu, marked by elevated serum levels of FGF-21, IL-6, hepatic TNF-α, as well as reduced IL-10 and adiponectin, was associated with steatosis- induced hepatic oxidative stress, reflected by increased hepatic MDA and decreased GSH levels, along with stimulated caspase-3 and decline in BcL-2 hepatic levels. These pathological disturbances were significantly ameliorated by taurine supplementation and evidenced histopathologically. The cross talk between hepatic FGF-21 and SIRT1 and their association to the induced perturbations are novel findings in this study. Taurine's efficacy in restoration of hepatic structure and function is partially via the increase in SIRT1 and associated reduction of FGF-21. Conclusion: The findings of the current study prove the protective role of taurine in NAFLD via a novel role in the amelioration of FGF-21/ SIRT1 axis, which could be considered a new therapeutic target.

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“…Deacetylation by SIRT1 leads to reduced levels of FOXA2 protein through increased degradation [25]. Small molecule sirtuin activators are under development, and their potential use in NAFLD treatment has been suggested [26]. …”

Section: Discussionmentioning

confidence: 99%

Transcription factor binding site enrichment analysis predicts drivers of altered gene expression in nonalcoholic steatohepatitis

Lake

Chaput

Novák

et al. 2016

Biochemical Pharmacology

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The molecular mechanisms behind the transition from simple steatosis to nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD) are not clearly understood. This hinders development of effective therapies for treatment and prevention of NASH. In this study expression profiling data from normal, steatosis, and NASH human livers was used to predict transcription factors that are misregulated as mechanistic features of NAFLD progression. Previously-published human NAFLD gene expression profiling data from normal, steatosis, and NASH livers was subjected to transcription factor binding site enrichment analysis. Selected transcription factors that bind enriched transcription factor binding sites were analyzed for changes in expression. Distinct transcription factor binding sites were enriched in genes significantly up-or down-regulated in NASH livers. Those enriched in up-regulated genes were bound by transcription factors such as FOXA, CEBP, and HNF1 family members, while those enriched in down-regulated genes were bound by nuclear receptors involved in xenobiotic sensing and lipid metabolism. Levels of mRNA and protein for selected transcription factors were significantly changed during disease progression. The study indicates that NAFLD progression involves changes in activity or expression of transcription factors that regulate genes involved in hepatic processes known to be altered in NASH. Transcription factors such as PPAR receptors, FoxA family members, and HNF4A might be targeted therapeutically to prevent NAFLD progression.

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A Potential Treatment of Non-Alcoholic Fatty Liver Disease with SIRT1 Activators

Cited by 85 publications

References 109 publications

Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats

Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats

A Novel Role of SIRT1/ FGF-21 in Taurine Protection Against Cafeteria Diet-Induced Steatohepatitis in Rats

Transcription factor binding site enrichment analysis predicts drivers of altered gene expression in nonalcoholic steatohepatitis

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