Plasma levels of SIRT1 associate with non-alcoholic fatty liver disease in obese patients

Mariani, Stefania; Fiore, Daniela; Basciani, Sabrina; Persichetti, Agnese; Contini, Savina; Lubrano, Carla; Salvatori, Luisa; Lenzi, Andrea; Gnessi, Lucio

doi:10.1007/s12020-014-0465-x

Cited by 103 publications

(77 citation statements)

References 41 publications

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“…Deng et al [41] reported a reduction of SIRT1 expression in rats with NAFLD induced by high-fat diets. In addition, Mariani et al [42] observed that SIRT1 expression was significantly decreased in visceral adipose tissue of morbidly obese patients with severe steatosis, compared to patients with slight or moderate steatosis. 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).…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Recent studies have shown a correlation between plasma SIRT1 and NAFLD in obese patients. SIRT1 levels were found to be significantly lower in an obese group with severe liver steatosis compared with a group with mild steatosis, and both groups had lower levels in the plasma compared with control lean patients [15,16]. It has long been known that obesity and NAFLD lead to ER stress and the UPR [17].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Ameliorates Lipid Droplet Accumulation in Liver Through a SIRT1/ ATF6-Dependent Mechanism

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Lipid droplets (LDs) are dynamic organelles that store neutral lipids during times of energy excess, and an increased accumulation of LDs in the liver is closely linked to hepatic steatosis. Our previous studies suggested that resveratrol (RSV) supplement could improve hepatic steatosis, but the underlying mechanism, particularly which related to LD accumulation, has not yet been elucidated. Methods: A high-fat diet (HFD) and palmitic acid were used to induce hepatic steatosis in mouse liver and hepatocytes, respectively. The effects of RSV on LD accumulation were analyzed in vivo and in vitro. The effects of RSV on the expression levels of LD-associated genes (ATF6, Fsp27β/CIDEC, CREBH, and PLIN1) were measured by qRT-PCR and western blot assays, followed by KD or overexpression of SIRT1 and ATF6 with small interfering RNAs or overexpressed plasmids, respectively. The dual luciferase reporter assay, chromatin immunoprecipitation assay, coimmunoprecipitation, and proximity ligation assay were utilized to clarify the mechanism of transcriptional regulation and possible interaction between SIRT1 and ATF6. Results: There was a significant increase in the accumulation of LDs in liver and hepatocytes during the process of HFD-induced steatosis, respectively, which was significantly inhibited by RSV supplementation. RSV notably activated SIRT1 expression and decreased the expression levels of ATF6, Fsp27β/CIDEC, CREBH, and PLIN1, which are associated with LD accumulation. Interestingly, the inhibitory effects of RSV on LD accumulation and the associated expression of genes in hepatocytes were abrogated or strengthened with SIRT1 silencing or overexpression, respectively. On the contrary, the benefits of RSV in hepatocytes were eliminated or aggravated when transfected with the overexpressed ATF6 or ATF6 siRNA, respectively. Furthermore, we found that RSV stimulated SIRT1 expression significantly, which was followed by increased deacetylation and inactivation of ATF6, resulting in a positive feedback loop for SIRT1 transcription associated with ATF6 binding to the SIRT1 promoter region. Conclusion: Taken together, these findings indicate that RSV supplementation improves hepatic steatosis by ameliorating the accumulation of LDs, and this might be partially mediated by a SIRT1/ATF6-dependent mechanism.

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“…These characteristics make SIRT1 a potent regulator of lifespan, metabolism and stress responses (Haigis & Sinclair, 2010;Houtkooper et al 2012). Both ageing and obesity negatively affect SIRT1 expression and activity (Pedersen et al 2008;dos Santos Costa et al 2010;Mariani et al 2015). Conversely, overexpression of SIRT1 mimics caloric restriction (Wood et al 2004), leading to a longer lifespan and resistance to obesity-related disorders in various animal models (Wood et al 2004;Milne et al 2007;Pfluger et al 2008).…”

Section: Introductionmentioning

confidence: 99%

SIRT1 overexpression attenuates offspring metabolic and liver disorders as a result of maternal high‐fat feeding

Nguyen

Chen

Zaky

et al. 2018

The Journal of Physiology

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Key points Maternal high‐fat diet (MHF) consumption led to metabolic and liver disorders in male offspring, which are associated with reduced sirtuin (SIRT)1 expression and activity in the offspring liver SIRT1 overexpression in MHF offspring reduced their body weight and adiposity and normalized lipid metabolic markers in epididymal and retroperitoneal adipose tissues SIRT1 overexpression in MHF offspring improved glucose tolerance, as well as systemic and hepatic insulin sensitivity SIRT1 overexpression ameliorated MHF‐induced lipogenesis, oxidative stress and fibrogenesis in the liver of offspring. Abstract Maternal obesity can increase the risk of metabolic disorders in the offspring. However, the underlying mechanism responsible for this is not clearly understood. Previous evidence implied that sirtuin (SIRT)1, a potent regulator of energy metabolism and stress responses, may play an important role. In the present study, we have shown, in C57BL/6 mice, that maternal high‐fat diet (HFD) consumption can induce a pre‐diabetic and non‐alcoholic fatty liver disease phenotype in the offspring, associated with reduced SIRT1 expression in the hypothalamus, white adipose tissues (WAT) and liver. Importantly, the overexpression of SIRT1 in these offspring significantly attenuated the excessive accumulation of epididymal (Epi) white adipose tissue (WAT) and retroperitoneal (Rp)WAT (P < 0.001), glucose intolerance and insulin resistance (both P < 0.05) at weaning age. These changes were associated with the suppression of peroxisome proliferator‐activated receptor gamma (PPAR)γ (P < 0.01), PPARγ‐coactivator 1‐alpha (P < 0.05) and sterol regulatory element‐binding protein‐1c in EpiWAT (P < 0.01), whereas there was increased expression of PPARγ in RpWAT (P < 0.05). In the liver, PPARγ mRNA expression, as well as Akt protein expression and activity, were increased (P < 0.05), whereas fatty acid synthase and carbohydrate response element binding protein were downregulated (P < 0.05), supporting increased insulin sensitivity and reduced lipogenesis in the liver. In addition, hepatic expression of endogenous anti‐oxidants, including glutathione peroxidase 1 and catalase, was increased (P < 0.01 and P < 0.05 respectively), whereas collagen and fibronectin deposition was suppressed (P < 0.01). Collectively, the present study provides direct evidence of the mechanistic significance of SIRT1 in maternal HFD‐induced metabolic dysfunction in offspring and suggests that SIRT1 is a promising target for fetal reprogramming.

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Plasma levels of SIRT1 associate with non-alcoholic fatty liver disease in obese patients

Cited by 103 publications

References 41 publications

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

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

Resveratrol Ameliorates Lipid Droplet Accumulation in Liver Through a SIRT1/ ATF6-Dependent Mechanism

SIRT1 overexpression attenuates offspring metabolic and liver disorders as a result of maternal high‐fat feeding

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