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Chicoric acid does not restore palmitate-induced decrease in irisin levels in PBMCs of newly diagnosed patients with T2D and healthy subjects

Targeting irisin as a myokine/adipokine is a new therapeutic approach in the improvement of insulin-resistance (IR) during type 2 diabetes (T2D). In present study we evaluated the effects of palmitate and chicoric acid (CA) on irisin production in peripheral blood mononuclear cells (PBMCs) of patients with T2D. This study performed on 20 newly diagnosed patients with T2D and 20 healthy subjects. PBMCs treated with palmitate and CA. PPARGC1A and FNDC5 genes expression assessed using qRT-PCR. Irisin levels in cell culture medium measured by ELISA. Palmitate decreased PPARGC1A and FNDC5 genes expression, as well as irisin levels in PBMCs from T2D and healthy volunteers. CA significantly restored palmitate-induced decrease in PPARGC1A gene expression in PBMCs of healthy subjects. Although, FNDC5 gene expression and irisin levels were not induced significantly by CA. In conclusion, palmitate decreases irisin production through down-regulation of PPARGC1A and FNDC5 expressions. However, CA does not effect on irisin pathway.Key points Palmitate reduced PPARGC1A and FNDC5 genes expression, as well as irisin secretion in PBMCs. Palmitate-induced decrease in PPARGC1A gene expression significantly has been reversed by CA in PBMCs of healthy subjects. CA did not return palmitate-decreased in FNDC5 gene expression and irisin levels in PBMCs

AMP‐activated protein kinase is a key regulator of obesity‐associated factors

An imbalance between caloric intake and energy expenditure leads to obesity. Obesity is an important risk factor for the development of several metabolic diseases including insulin resistance, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. So, controlling obesity could be effective in the improvement of obesity-related diseases. Various factors are involved in obesity, such as AMP-activated protein kinases (AMPK), silent information regulators, inflammatory mediators, oxidative stress parameters, gastrointestinal hormones, adipokines, angiopoietin-like proteins, and microRNAs. These factors play an important role in obesity by controlling fat metabolism, energy homeostasis, food intake, and insulin sensitivity. AMPK is a heterotrimeric serine/threonine protein kinase known as a fuel-sensing enzyme. The central role of AMPK in obesity makes it an attractive molecule to target obesity and related metabolic diseases. In this review, the critical role of AMPK in obesity and the interplay between AMPK and obesity-associated factors were elaborated

The level of gene expression of Bax and Bcl-2 and the activity of caspase 3 in the liver tissues of normal, type 1 and type 2 diabetic rats before and after treatment with aqueous extract of garlic

Introduction: One of the complications of diabetes mellitus is induction of apoptosis in liver tissues. Activation of caspase 3 caused apoptosis in the cells. Garlic is a most common plant in diet that its effect on apoptosis was not determined. In this study the effects of this extract on Bax and Bcl-2 gene expression and the activity of caspase 3, were determined in type 1 and 2 of diabetes in rats. Methods: Wistar rats divided into six groups included normal control rats, diabetes type 1 (D1), diabetes type 1 treated with garlic extract (D1G), diabetes type 2 (D2), diabetes type 2 treated with garlic extract (D2G) and garlic control (G). At the end of treatment time, liver tissues were removed quickly and stored in -70 °C. For evaluation of gene expression, RNA extraction, cDNA synthesis and Real time PCR were done. The activity of caspase 3 was determined with flourometric method. Results: The level of gene expression of Bax and Bcl-2, did not change significantly in different groups. The activity of caspase 3 in D1 rats, increased significantly compared to the control rats(p=0.003). The activity of this enzyme was high in D1G compared to control rats yet (p=0.021). In D2, D2G and G groups, caspase activity was not changed in comparison with the control rats Conclusion: Diabetes mellitus type1 caused apoptosis in rat livers, but garlic extract cannot ameliorate it

Chicoric acid ameliorates palmitate-induced sphingosine 1-phosphate signaling pathway in the PBMCs of patients with newly diagnosed type 2 diabetes

Objective Sphingosine 1-phosphate (S1P) signaling pathway is involved in the pathogenesis of type 2 diabetes (T2D). So, targeting S1P signaling pathway could be considered as potential therapeutic target for T2D. The aim of this study was to investigate the effects of palmitate and chicoric acid (CA) on S1P signaling pathway in peripheral blood mononuclear cells (PBMCs) from newly diagnosed patients with T2D. Materials and methods 20 newly diagnosed patients with T2D, aged 40-60 years, were enrolled in the study. PBMCs were isolated and then treated as follows: control groups (untreated, treated with BSA 1% for 12 h), CA groups (treated with 50 mu M CA for 6 h), palmitate groups (treated with 500 mu M palmitate for 12 h), palmitate + CA groups (treated with 500 mu M palmitate for 12 h and then treated with 50 mu M CA for 6 h). Finally, sphingosine kinase 1 (SPHK1) and sphingosine 1-phosphate receptor 1 (S1PR1) genes expression were evaluated by real-time PCR and S1PR1 protein levels were quantified using ELISA. Results Palmitate significantly increased SPHK1 and S1PR1 genes expression and S1PR1 protein levels in PBMCs of patients with diabetes. However, CA ameliorates palmitate-increased SPHK1 and S1PR1 genes expression and S1PR1 levels in these cells. Conclusion These data indicate that CA could be considered as a novel S1P signaling pathway inhibitor through down regulation of SPHK1 and S1PR

Non-Alcoholic Steatohepatitis and Autoimmune Hepatitis Cirrhosis May Have a Higher Risk of Progression to Hepatocellular Carcinoma

Background: The evaluation of different cell proliferation and apoptosis indicators in cirrhotic tissues caused by different injuries may help recognize the etiology of cirrhosis and the risk of progression to hepatocellular carcinoma. Objectives: This study aimed to measure p53 gene expression and AMPK and pAMPK protein expressions, as well as AgNOR features in cirrhotic tissues associated with five different etiologies in comparison with simple hepatic steatosis and controls. Methods: In this case-control study, AMPK and PAMPK protein expressions, p53 gene expression, and AgNOR features were investigated in 68 cirrhotic liver tissues obtained from patients with NASH (n = 15), HBV/HCV (n = 14), AIH (n = 15), PSC (n = 15), and alcohol toxicity (n = 9) and compared with tissues from individuals with simple steatosis (n = 15) and control subjects (n = 15). Protein and gene expressions were determined using western blotting and quantitative real-time polymerase chain reaction, respectively. Silver nitrate staining was used to assess AgNOR features. Results: Significantly higher levels of AMPK and pAMPK were detected in all cirrhotic tissues compared to controls (P < 0.05). Also, a significantly and simultaneously higher p53 gene expression (P < 0.01) and AgNOR features, including total AgNOR length (TAL) (P < 0.001), total AgNOR number (TAN) (P < 0.01), and total AgNOR area (TAA) (P < 0.01), was detected in the hepatic cirrhotic tissues obtained from patients with PSC, NASH, and AIH. There was a significant positive correlation between p53 gene expression and AgNOR features in cirrhotic tissues (P < 0.01). Conclusions: Increased AMPK and pAMPK protein levels may be a general response to cirrhosis. Cirrhotic patients diagnosed with AIH, PSC, and NASH have a higher risk of progressing to hepatocellular carcinoma than those diagnosed with viral and alcoholic cirrhosi

Chlorella vulgaris supplementation attenuates the progression of liver fibrosis through targeting TGF-β-signaling pathway in the CCl4-induced liver fibrosis in rats

The purpose of this study is to investigate the molecular mechanism underlying hepatoprotective effect of Chlorella vulgaris extract (CVE). The administration of both doses of CVE attenuated liver damage and decreased serum markers and oxidative stress parameters dramatically. Also, CVE treatment downregulated hepatic gene expression of collagen type1 (Col1a1), fibronectin (Fn1), transforming growth factor-beta 1 (Tgfb1), transforming growth factor-beta receptor 2 (Tgfbr2) and SMAD family member 3 (Smad3) significantly. Hepatic level of TGF-β1 protein was decreased by CVE treatment significantly. CVE supplementation restraints liver fibrosis progression through amelioration of oxidative stress status and targeting TGF-β signaling pathway. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group

Chlorella vulgaris supplementation attenuates the progression of liver fibrosis through targeting TGF-β-signaling pathway in the CCl4-induced liver fibrosis in rats

The purpose of this study is to investigate the molecular mechanism underlying hepatoprotective effect of Chlorella vulgaris extract (CVE). The administration of both doses of CVE attenuated liver damage and decreased serum markers and oxidative stress parameters dramatically. Also, CVE treatment downregulated hepatic gene expression of collagen type1 (Col1a1), fibronectin (Fn1), transforming growth factor-beta 1 (Tgfb1), transforming growth factor-beta receptor 2 (Tgfbr2) and SMAD family member 3 (Smad3) significantly. Hepatic level of TGF-β1 protein was decreased by CVE treatment significantly. CVE supplementation restraints liver fibrosis progression through amelioration of oxidative stress status and targeting TGF-β signaling pathway