SummarySirtuins are members of the silent information regulator 2 (Sir2) family, a group of Class III histone/protein deacetylases. There are 7 different sirtuins in mammals (SIRT1-7), of which SIRT1 is the best known and most studied. SIRT1 is responsible for the regulation of protein activation by means of deacetylating a variety of proteins that play important roles in the pathophysiology of metabolic diseases. Recently, it has been shown that SIRT1 plays key roles in the regulation of lipid and glucose homeostasis, control of insulin secretion and sensitivity, antiinflammatory effects, control of oxidative stress and the improvements in endothelial function that result due to increased mitochondrial biogenesis and β-oxidation capacity.Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease, and it has been accepted as the hepatic component of metabolic syndrome. Recent studies have shown that SIRT expression in the liver is significantly decreased in an NAFLD model of rats fed a high-fat diet, and moderate SIRT1 overexpression protects mice from developing NAFLD. In addition to resveratrol, a natural SIRT1 activator, small-molecule pharmacologic SIRT1 activators have positive effects on metabolic diseases. These effects are particularly promising in the case of diabetes mellitus, for which phase studies are currently being performed. With this information, we hypothesized that the pharmacologic activation of SIRT1, which has been implicated in the pathogenesis of NAFLD, will be a potential therapeutic target for treating NAFLD. In this paper, we review the metabolic effects of SIRT1 and its association with the pathophysiology of NAFLD.

In this study, we aimed to evaluate the endothelial functions in patients with nonalcoholic fatty liver disease (NAFLD). In this observational case-control study, a total of 51 patients with NAFLD in study group and a total of 21 with age- and sex-equivalent individuals in control group were enrolled. In both patients and control groups, levels of asymmetric dimethylarginine (ADMA), systemic endothelial function (brachial artery flow-mediated dilation) (FMD) and carotid artery intima-media thickness (C-IMT) were measured. FMD and C-IMT were evaluated by vascular ultrasound. Plasma levels of ADMA were measured by ELISA. C-IMT was significantly higher in patients with NAFLD group than control group (0.67 ± 0.09 vs. 0.52 ± 0.11 mm, P < 0.001). The average C-IMT measurements were found in groups of control, simple steatosis, and NAFLD with (borderline and definite) NASH as 0.52 ± 0.11, 0.63 ± 0.07, and 0.68 ± 0.1 mm, respectively. The differences between groups were significant (P < 0.001). Measurement of brachial artery FMD was significantly lower in patients with NAFLD group compared to control group (7.3 ± 4.8 vs. 12.5 ± 7.1 %, P < 0.001). FMD measurements in groups of control, the simple steatosis, and NAFLD with NASH as 12.5 ± 7.1, 9.64 ± 6.63, and 7.03 ± 4.57 %, respectively, and the differences were statistically significant (P < 0.001). The increase in C-IMT and decrease in FMD was independent from metabolic syndrome and it was also more evident in patients with simple steatosis and NASH compared to control group. There was no significant difference between the control and NAFLD groups in terms of plasma ADMA levels (0.61 ± 0.11 vs. 0.69 ± 0.37 μmol/L, P = 0.209). Our data suggested that NAFLD is associated with endothelial dysfunction and increased earlier in patients with atherosclerosis compared to control subjects.

Although subject to future confirmation, our data suggest that hepcidin levels are elevated in NAFLD and could be associated with lipid parameters in this setting.

Serum IGFBP-5 levels may be useful to differentiate both advanced fibrosis and definite nonalcoholic steatohepatitis from other NAFLD groups. Also, serum IGF-1 levels may be useful to differentiate advanced fibrosis in patients with NAFLD.

Background: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. Subjects and methods: We measured serum progranulin levels in 95 patients with biopsy-proven NAFLD and 80 age- and sex-matched controls. The potential associations between progranulin and the characteristics of NAFLD patients were examined by multiple linear regression analysis. Results: Serum progranulin levels were significantly higher in NAFLD patients (34 ± 13 ng/mL) than in controls (28 ± 7 ng/mL, P < 0.001). In NAFLD patients, serum progranulin levels were associated with lipid levels and the degree of hepatic fibrosis. After adjustment for potential confounders, serum progranulin remained an independent predictor of the degree of hepatic fibrosis in NAFLD patients (β = 0.392; t =2.226, P < 0.01). Conclusions: Compared with controls, NAFLD patients have higher serum progranulin concentrations, which are closely associated with lipid values and the extent of hepatic fibrosis.

Background/AimsWe sought to examine whether the presence of gallstone disease (GD) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) is associated with liver fibrosis and histological nonalcoholic steatohepatitis (NASH) score.MethodsWe included 441 Turkish patients with biopsy-proven NAFLD. GD was diagnosed in the presence of sonographic evidence of gallstones, echogenic material within the gallbladder with constant shadowing and little or no visualization of the gallbladder or absence of gallbladder at ultrasonography, coupled with a history of cholecystectomy.ResultsFifty-four patients (12.2%) had GD (GD+ subjects). Compared with the GD- subjects, GD+ patients were older, had a higher body mass index and were more likely to be female and have metabolic syndrome. However, GD+ patients did not have a higher risk of advanced fibrosis or definite NASH on histology. After adjustment for potential confounding variables, the prevalence of GD in NAFLD patients was not associated with significant fibrosis (≥2) (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.53 to 2.21; p=0.68) or definite NASH (OR, 1.03; 95% CI, 0.495 to 2.12; p=0.84).ConclusionsThe presence of GD is not independently associated with advanced fibrosis and definite NASH in adult Turkish patients with biopsy-proven NAFLD.

Our findings indicate that EFT and C-IMT were significantly higher in patients with NAFLD compared with the controls and waist circumference and C-IMT are independent predictors for EFT in patients with NAFLD.

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