mRNA Expression Levels Of SIRT1 Research Articles

Effects of oleoylethanolamide supplementation on the expression of lipid metabolism-related genes and serum NRG4 levels in patients with non-alcoholic fatty liver disease: A randomized controlled trial

This study investigated the effects of oleoylethanolamide (OEA) supplementation on the expression levels of SIRT1, AMPK, PGC-1α, PPAR-γ, CEBP-α and CEBP-β genes and serum neuregulin 4 (NRG4) levels in patients with non-alcoholic fatty liver diseases (NAFLD). Sixty obese patients with NAFLD were equally allocated into either OEA or placebo group for 12 weeks. The mRNA expression levels of genes were determined using the reverse transcription polymerase chain reaction (RT-PCR) technique. Serum NRG4 level was also assessed using an enzyme-linked immunosorbent assay (ELISA) kit. At the endpoint, mRNA expression levels of SIRT1(p=0.001), PGC-1α (p=0.011) and AMPK (p=0.019) were significantly higher in the OEA group compared to placebo group. However, no significant differences were observed in the expression levels of PPAR-γ, CEBP-α and CEBP-β between the two groups. Serum NRG4 levels significantly increased in the OEA group compared with the placebo group after controlling for confounders (p=0.027). In the OEA group, significant relationships were found between percent of changes in the expression levels of the SIRT1, AMPK and PGC-1α as well as serum NRG4 level with percent of changes in some anthropometric measures. Moreover, in the intervention group, percent of changes in high-density lipoprotein cholesterol was positively correlated with percent of changes in the expression levels of the SIRT1 and AMPK. While, percent of changes in triglyceride was inversely correlated with percent of changes in the expression levels of SIRT1. OEA could beneficially affect expression levels of some lipid metabolism-related genes and serum NRG4 level. "REGISTERED UNDER IRANIAN REGISTRY OF CLINICAL TRIALS IDENTIFIER NO: IRCT20090609002017N32".

Cognitive Performance during the Development of Diabetes in the Zucker Diabetic Fatty Rat.

Increased insulin levels may support the development of neural circuits involved in cognition, while chronic mild inflammation may also result in cognitive impairment. This study aimed to gain more insight into whether cognition is already impacted during adolescence in a genetic rat model for obesity and type 2 diabetes. Visual discrimination learning throughout adolescence and the level of motivation during early adulthood were investigated in Zucker Diabetic Fatty (ZDF) obese and ZDF lean rats using operant touchscreens. Blood glucose, insulin, and lipids were longitudinally analyzed. Histological analyses were performed in the liver, white adipose tissues, and the prefrontal cortex. Prior to the experiments with the genetic ZDF research model, all experimental assays were performed in two groups of outbred Long Evans rats to investigate the effect of different feeding circumstances. Adolescent ZDF obese rats outperformed ZDF lean rats on visual discrimination performance. During the longitudinal cognitive testing period, insulin levels sharply increased over weeks in ZDF obese rats and were significantly enhanced from 6 weeks of age onwards. Early signs of liver steatosis and enlarged adipocytes in white adipose tissue were observed in early adult ZDF obese rats. Histological analyses in early adulthood showed no group differences in the number of prefrontal cortex neurons and microglia, nor PSD95 and SIRT1 mRNA expression levels. Together, our data show that adolescent ZDF obese rats even display enhanced cognition despite their early diabetic profile.

Melatonin restores the declining maturation quality and early embryonic development of oocytes in aged mice

With increase in women's age, the reproductive capability of female mammals decreases dramatically caused by age-related oxidative stress, coinciding with the decline in the ovarian reserve, and the quality and quantity of oocytes, which is the main determinant of female fertility. Melatonin, as an effective antioxidant and antiaging substance, is secreted by the pineal gland and been found in the follicular fluid as well, which has been turned out to enable to protect oocytes from oxidative stress during ovulation. However, the beneficial effects of melatonin on meiotic maturation in vitro and early embryo development of aged oocytes are still not fully understood. Thus, the aim of this study is to explore the potential mechanism of melatonin to improve the oocytes maturation and early embryonic development. The results suggested that oocyte quality decreased with age, whereas 10−6 M melatonin supplementation can significantly prompt the maturation quality of oocytes, the rate of fertilization and the formation rate of blastocyst. Mechanistic investigation indicated that melatonin supplementation not only restored the function of mitochondria by reducing reactive oxygen species (ROS) generation and early apoptosis, but also increased the level of ATP and total GSH through enhancing the mRNA expression levels of SIRT1, SIRT3, GPX4, SOD1 and SOD2. In conclusion, melatonin could alleviate the impairment of age-related oxidative stress to meiotic maturation and early embryonic development of oocytes. This study may provide a potential remediation strategy to improve the quality of oocytes from aged women and the efficiency of assisted reproductive technologies.

Curcumenol improves renal function in 5/6 nephrectomy-induced chronic renal failure rats via the SIRT1/NF-κB pathway.

The present work aimed to explore the protective effects of curcumenol and evaluate its pharmacological mechanisms in 5/6 nephrectomy-induced chronic renal failure (CRF). Rats with CRF were administrated curcumenol and the effects on renal functions were investigated. Renal function examinations were carried out, whereas serum levels of inflammatory mediators, including NF-κB, MCP-1 and IL-1β were analyzed by ELISA. The mRNA expression levels of SIRT1, p65 and IκBα were measured by qRT-PCR, and the SIRT1 protein levels were analyzed by western blot and immunohistochemistry. Our results indicated that curcumenol significantly improved the renal functions in the CRF rats. Compared to the sham group, serum levels of NF-κB, MCP-1, IL-1β, and the mRNA expression levels of p65 were significantly increased (p < 0.01), whereas the mRNA expression level of IκBα was significantly decreased (p < 0.01) and the SIRT1 levels were dramatically down-regulated (p < 0.05) in the CRF groups. Treatment with curcumenol remarkably inhibited inflammatory responses as reflected by the reduced levels of inflammatory mediators (p < 0.01) and SIRT1 up-regulation (p < 0.05). Our findings suggested that curcumenol could improve the renal function in 5/6 nephrectomy-induced CRF rats, and the mechanisms might involve suppressing the associated inflammation and modulating the SIRT1 and NF-κB signaling pathways.

Phellopterin cream exerts an anti-inflammatory effect that facilitates diabetes-associated cutaneous wound healing via SIRT1

BackgroundDiabetic ulcers, which are characterized by chronic nonhealing wounds with a long-lasting inflammatory state, are a typical symptom in individuals with diabetes, and there is still no effective treatment for these lesions. Angelica dahurica plays a critical role in inflammatory diseases. Among numerous monomeric compounds, phellopterin has been shown to have anti-inflammatory properties. PurposeTo research the bioactive constituents in Angelica dahurica and their mechanism of action in treating diabetic ulcers. Study designChemical research of Angelica dahurica led to the identification of a new coumarin, dahuricoumarin A (1), along with seven known compounds (2 − 8). All compounds were tested for anti-inflammatory activity, and phellopterin, compound (3), significantly decreased the expression of intercellular cell adhesion molecule-1 (ICAM-1), a representative indicator of inflammation. Phellopterin can also increase SIRT1 protein, a key target for inflammation. In our research, we confirmed the anti-inflammatory effects of phellopterin on diabetic ulcers and explored the underlying mechanism of action. MethodsThe expression of IFN-γ, SIRT1, and ICAM-1 in human diabetic ulcer tissues was studied using immunohistochemistry. Streptozotocin was used to induce a diabetic model in C57BL/6J mice, and ulcers were surgically introduced. After phellopterin treatment, the skin lesions of diabetic mice were observed over a period of time. The protein and mRNA expression levels of SIRT1 and ICAM-1 were measured using H&E, qRT–PCR and immunohistochemical staining. A HaCaT cell inflammatory model was induced by IFN-γ. Using a lentiviral packaging technique, MTT assay, and Western blotting, the effect of phellopterin on the proliferation of HaCaT cells and the expression of ICAM-1 was evaluated under normal and SIRT1 knockdown conditions. ResultsHigh levels of ICAM-1 and IFN-γ were identified, but low levels of SIRT1 were found in human diabetic ulcer tissues, and phellopterin showed therapeutic benefits in the healing process by attenuating chronic inflammation and promoting re-epithelialization, along with SIRT1 upregulation and ICAM-1 downregulation. However, inhibiting SIRT1 reversed its proliferative and anti-inflammatory effects. ConclusionIn vitro and in vivo, phellopterin exerts anti-inflammatory and proliferative effects that promote diabetic wound healing, and the potential mechanism depends on SIRT1.

Aerobic Exercise Improves Pulmonary Fibrosis by Improving Insulin Resistance and Inflammation in Obese Mice.

BackgroundPrevious studies have demonstrated that obesity is associated with pulmonary fibrosis. We attempted to identify whether regular aerobic exercise (AE) can protect against high-fat diet (HFD)-associated pulmonary fibrosis.MethodsForty-eight C57BL/6 mice were randomly assigned to four groups: chow group (Ch), chow plus exercise group (CE), obesity group (Ob), and obesity plus exercise group (OE). The mice were fed either an HFD or a chow diet for 16 weeks, and low-intensity aerobic exercise (AE) was performed in the last 8 weeks. We measured the degree of pulmonary fibrosis; pulmonary inflammation; oxidative stress parameters; insulin resistance-related indicators; the number of inflammatory cells in bronchoalveolar lavage fluid (BALF); the mRNA expression levels of IL-10, IL-1β, TGF-β, TNF-α, CXCL-1, IL-17, MMP-9, MPO, NE, and sirt-1; and the BALF levels of CXCL-1, IL-17, TGF-β, IL-10, IL-1β, and TNF-α in lung tissue.ResultsAE in obese mice protected against obesity-associated pulmonary fibrosis, chronic inflammation, pro-oxidative/antioxidative imbalance, and insulin resistance. AE ameliorated the HFD-induced inflammatory response and neutrophil infiltration in the lung. AE downregulated BALF levels of CXCL-1, IL-1β, TNF-α IL-17, and TGF-β but upregulated BALF levels of IL-10. AE decreased IL-1β, TGF-β, TNF-α, CXCL-1, IL-17, MMP-9, MPO, and NE mRNA expression levels but upregulated IL-10 and sirt-1 mRNA expression levels in the lung.ConclusionsAE protects against HFD-induced pulmonary fibrosis by improving obesity-associated insulin resistance, chronic low-grade inflammation, and pro-oxidative/antioxidative imbalance. AE improved HFD-induced pulmonary fibrosis by suppressing IL-17, TGF-β, NE, and MMP-9 expression and activating IL-10 and sirt-1 expression.

Panax notoginseng saponins reverse P-gp-mediated steroid resistance in lupus: involvement in the suppression of the SIRT1/FoxO1/MDR1 signalling pathway in lymphocytes

BackgroundP-glycoprotein (P-gp)-mediated steroid resistance (SR) has been suggested to play a significant role in lupus nephritis (LN) treatment failure. Panax notoginseng saponins (PNS), the main effective components of the traditional Chinese medicine notoginseng, exhibited potent reversal capability of P-gp-mediated SR, but its mechanism remains unknown. This study aimed to investigate the effect of PNS on reversing SR in lupus and its underlying mechanism in vivo and in vitro.MethodsIn this study, an SR animal and splenic lymphocyte model were established using low-dose methylprednisolone (MP). Flow cytometry was used to detect the effect of PNS on reversing P-gp-mediated SR and the expression of P-gp in different T-cells phenotypes. Serum levels of ANA and dsDNA in lupus mice were measured by ELISA. Apoptosis was identified by Annexin V-FITC/PI staining. RT–PCR and Western blotting were used to detect the protein and mRNA expression levels of SIRT1, FoxO1, and MDR1 in SR splenic lymphocytes from lupus mice (SLCs/MPs).ResultsPNS could reverse the SR in lupus mice. Simultaneously, PNS increased the apoptotic effect of MP on SLCs/MP cells. The increased accumulation of rhodamine-123 (Rh-123) indicated that intracellular steroid accumulation could be increased by the action of PNS. Moreover, PNS decreased the expression of P-gp levels. Further experiments elucidated that the SIRT1/FoxO1/MDR1 signalling pathway existed in SLCs/MP cells, and PNS suppressed its expression level to reverse SR. The expression of P-gp in Th17 from SLCs/MP cells was increased, while PNS could reduce its level in a more obvious trend.ConclusionThe present study suggested that PNS reversed P-gp-mediated SR via the SIRT1/FoxO1/MDR1 signalling pathway, which might become a valuable drug for the treatment of SR in lupus. Th17 might be the main effector cell of PNS reversing SR.

Nephroprotective activity of Aframomum melegueta seeds extract against diclofenac-induced acute kidney injury: A mechanistic study

Ethnopharmacological relevanceIn Africa, Aframomum species have been traditionally used to treat illnesses such as inflammation, hypertension, diarrhea, stomachache and fever. Moreover, Aframomum melegueta seed extracts (AMSE) are used in traditional medicine to relieve stomachaches and inflammatory diseases. AimChronic administration of diclofenac (DIC) has been reported to cause acute kidney injury (AKI), which is a serious health condition. The nephroprotective effect of AMSE is yet to be elucidated. Accordingly, this study aims to investigate the phytoconstituents of standardized AMSE, evaluate its nephroprotective effects against DIC-induced AKI in rats, and elaborate its underlying molecular mechanisms. Materials and methodsThe quantitative estimation of major AMSE constituents and profiling of its secondary metabolites were conducted via RP-HPLC and LC-ESI/Triple TOF/MS, respectively. Next, DIC (50 mg/kg)-induced AKI was achieved in Sprague-Dawley rats and DIC-challenged rats were administered AMSE (100 and 200 mg/kg) orally. All treatments were administered for five consecutive days. Blood samples were collected and the sera were used for estimating creatinine, urea and, kidney injury molecule (KIM)-1 levels. Kidney specimens were histopathologically assessed and immunohistochemically examined for c-Myc expression. A portion of the kidney tissue was homogenized and examined for levels of oxidative stress markers (MDA and GSH). Heme oxygenase (HO)-1, TNF-α, IL-6, Bax, Bcl2 and caspase-3 renal levels were quantified by ELISA. Moreover, the protein expression levels of NF-ҡB p65 was quantified using Western blot analysis, whereas mRNA expression levels of AMPK, SIRT-1, nuclear factor erythroid-2-related factor (Nrf2) and STAT3 were detected using qRT-PCR in the remaining kidney tissues. ResultsStandardized AMSE was shown to primarily contain 6-gingerol, 6-shogaol and 6-paradol among the 73 compounds that were detected via LC-ESI/Triple TOF/MS including phenolic acids, hydroxyphenylalkanes, diarylheptanoids and fatty acids. Relative to DIC-intoxicated rats, AMSE modulated serum creatinine, urea, KIM-1, renal MDA, TNF-α, IL-6, Bax, and caspase-3 levels. AMSE has also improved renal tissue architecture, enhanced GSH and HO-1 levels, and upregulated renal Nrf2, AMPK, and SIRT-1 mRNA expression levels. Furthermore, AMSE suppressed NF–ҡB p65 protein and STAT3 mRNA expression, and further reduced c-Myc immunohistochemical expression in renal tissues. Overall, our findings revealed that AMSE counteracted DIC-induced AKI via its antioxidant, anti-inflammatory, and antiapoptotic activities. Moreover, AMSE activated Nrf2/HO1 and AMPK/SIRT1, and inhibited NF-ҡB/STAT3 signaling pathways. Therefore, AMSE is a promising agent for inhibiting DIC-induced nephrotoxicity.

Long non-coding RNA MCM3AP-AS1 protects chondrocytes ATDC5 and CHON-001 from IL-1β-induced inflammation via regulating miR-138-5p/SIRT1

ABSTRACT Osteoarthritis (OA) is a chronic inflammatory joint disease. Increased apoptosis of chondrocytes contributes to cartilage degradation in OA pathogenesis. The function of lncRNA MCM3AP-AS1 in regulating the viability of chondrocytes still awaits further elaboration. In this work, MCM3AP-AS1, miR-138-5p and SIRT1 mRNA expression levels in OA and normal cartilage tissues were detected by qRT-PCR. Besides, chondrocyte cell lines, CHON-001 and ATDC5 induced by interleukin-1β (IL-1β) were used to initiate the inflammatory response environment of OA. CCK-8 assay was used to examine the cell multiplication; meanwhile, transwell assay was utilized to detect migration. Western blot was adopted to determine SIRT1 expression in chondrocyte. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate inflammatory factor levels. In addition, the binding sites between MCM3AP-AS1 and miR-138-5p, miR-138-5p and 3ʹUTR of SIRT1 were validated by dual-luciferase reporter assay, RIP assay or RNA pull-down assay. It was found that MCM3AP-AS1 was declined in OA cartilage tissues, positively interrelated with SIRT1 expression while negatively correlated with miR-138-5p. MCM3AP-AS1 up-regulation enhanced the viability and migration of CHON-001 and ATDC5 cells while restraining the apoptosis and inflammatory response. Additionally, miR-138-5p overexpression counteracted the effects on chondrocytes caused by MCM3AP-AS1 overexpression. MCM3AP-AS1 could adsorb miR-138-5p, and SIRT1 was verified as a target of miR-138-5p, and SIRT1 could be up-regulated by overexpression of MCM3AP-AS1 indirectly. In conclusion, MCM3AP-AS1 has the potential to be the ‘ceRNA’ to regulate miR-138-5p and SIRT1 in chondrocytes, and to participate in the pathogenesis of OA.

Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington\u2019s Disease

The potential role of Sirt1 and Sirt2 subtypes of Sirtuins (class III NAD+-dependent deacetylases) in the pathogenesis of Huntington’s disease (HD) has been extensively studied yielding some controversial results. However, data regarding the involvement of Sirt3 and their variants in HD are considerably limited. The aim of this study was to assess the expression pattern of Sirt1 and three Sirt3 mRNA isoforms (Sirt3-M1/2/3) in the striatum, cortex and cerebellum in respect of the effect of gender, age and the presence of the transgene using the N171-82Q transgenic mouse model of HD. Striatal, cortical and cerebellar Sirt1-Fl and Sirt3-M1/2/3 mRNA levels were measured in 8, 12 and 16 weeks old N171-82Q transgenic mice and in their wild-type littermates. Regarding the striatum and cortex, the presence of the transgene resulted in a significant increase in Sirt3-M3 and Sirt1 mRNA levels, respectively, whereas in case of the cerebellum the transgene resulted in increased expression of all the assessed subtypes and isoforms. Aging exerted minor influence on Sirt mRNA expression levels, both in transgene carriers and in their wild-type littermates, and there was no interaction between the presence of the transgene and aging. Furthermore, there was no difference between genders. The unequivocal cerebellar Sirtuin activation with presumed compensatory role suggests that the cerebellum might be another key player in HD in addition to the most severely affected striatum. The mitochondrially acting Sirt3 may serve as an interesting novel therapeutic target in this deleterious condition.

Resveratrol Reduces Oxidative Stress and Apoptosis in Podocytes via Sir2-Related Enzymes, Sirtuins1 (SIRT1)/Peroxisome Proliferator-Activated Receptor γ Co-Activator 1α (PGC-1α) Axis.

BackgroundPGC-1α can be activated by deacetylation reactions catalyzed by SIRT1. Resveratrol is currently known as a potent activator of SIRT1. However, it is unknown whether the renal-protective effect of resveratrol is further related to activation of the podocyte SIRT1/PGC-1α pathway.Material/MethodsHigh glucose was used to stimulate mouse podocytes. Resveratrol and PGC-1α siRNA transfection were used to perform co-intervention treatments. The protein and mRNA expression levels of SIRT1, PGC-1α, NRF1, and TFAM were detect by immunofluorescence, Western blot analysis, and qRT-PCR in the podocytes, respectively. DCHF-DA and MitoSOX™ staining were used to monitor the total ROS and mitochondrial ROS levels, respectively. The specific activities of complexes I and III were measured using Complex I and III Assay Kits. Mitochondrial membrane potential and cell apoptosis were measured using JC-1 staining and Annexin V-FITC/PI double-staining, respectively.ResultsWe found that high-glucose stimulation results in time-dependent decreases in the expression of SIRT1, PGC-1α, and its downstream genes NRF1 and mitochondrial transcription factor A (TFAM) for mouse podocytes, and increases ROS levels in cells and mitochondria. Moreover, the expression of nephrin was downregulated and the cell apoptotic rate was increased. Resveratrol treatment can improve abnormalities caused by high-glucose stimulation. In addition, it can also reduce the release of mitochondrial cytochrome C and DIABLO proteins to the cytoplasm and increase respiratory chain complex I and III activity and mitochondrial membrane potential.ConclusionsResveratrol can reduce the oxidative damage and apoptosis of podocytes induced by high-glucose stimulation via SIRT1/PGC-1α-mediated mitochondrial protection.

MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1

MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as critical gene regulators by targeting mRNAs for translational repression or degradation. In this study, we showed that the expression level of miR-133b was decreased, while Sirt1 mRNA expression levels were increased in hepatocellular carcinoma (HCC) and cell lines, and we identified Sirt1 as a novel direct target of miR-133b. The over-expression of miR-133b suppressed Sirt1 expression. In addition, miR-133b over-expression resulted in attenuating HCC cell proliferation and invasion together with apoptosis increase in vitro. HepG2 cell transplantation revealed that up-regulation of miR-133b could inhibit HCC tumor genesis in vivo. Forced expression of Sirt1 partly rescued the effect of miR-133b in vitro. Furthermore, our study showed that miR-133b over-expression or Sirt1 down-regulation elevated E-cadherin expression, and repressed glypican-3 (GPC3) and the anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1) expression. The inhibition of GPC3 expression repressed Bcl-2, Bcl-xL, and Mcl-1 expression, and elevated E-cadherin expression. Moreover, the Sirt1 up-regulation resulted in increases in HCC cell proliferation and invasion together with decreases apoptosis, and increases in the cytosolic accumulation and nuclear translocation of the transcription factor β-catenin in vitro. But the effect of Sirt1 up-regulation was partly reversed by GPC3 down-regulation in vitro. Taken together, these findings provide insight into the role and mechanism of miR-133b in regulating HCC cell proliferation, invasion and apoptosis via the miR-133b/Sirt1/GPC3/Wnt β-catenin axis, and miR-133b may serve as a potential therapeutic target in HCC in the future.

Des-acyl ghrelin protects microvascular endothelial cells from oxidative stress-induced apoptosis through sirtuin 1 signaling pathway

ObjectiveGhrelin is a stomach-derived hormone. Acylation of ghrelin has been essential for its biological activities such as stimulating appetite. On the other hand, the function of des-acyl ghrelin (Des-G) has not been fully elucidated. The aim of the present study is to examine the anti-apoptotic effect of Des-G on endothelial cells. Materials/MethodsAfter human retinal microvascular endothelial cells (RMECs) were pretreated with or without 100nmol/L Des-G, apoptosis was induced with 0.1mmol/L hydrogen peroxide (H2O2). For pharmacological inhibition of surtuin 1 (SIRT1) catalytic activity, the cells were treated with 10μmol/L Ex-527. Inhibition of SIRT1 with siRNA was also performed. The quantitative estimation of DNA fragmentation was used as a marker of apoptosis. Furthermore, total SIRT activity in nuclear extracts, mRNA and protein levels of SIRT1, manganese superoxide dismutase (MnSOD) and catalase were determined. ResultsDes-G pretreatment protected RMECs from oxidative stress-induced apoptosis and increased SIRTs deacetylase activity in nuclear extracts. On the other hand, both pharmacological and siRNA mediated inhibition of SIRT1 attenuated the anti-apoptotic effect of Des-G. Moreover, Des-G increased mRNA and protein levels of SIRT1 and antioxidant enzymes such as MnSOD and CAT, which are downstream targets of SIRT1. Although the treatment of Ex-527 did not alter mRNA expression levels of SIRT1, it decreased mRNA expression levels of antioxidant enzymes in the cells with Des-G pretreatment. ConclusionsOur results suggest that SIRT1 signaling pathway contributes to protective effect of Des-G against oxidative stress-induced apoptosis.

Adipose tissue and liver expression of SIRT1, 3, and 6 increase after extensive weight loss in morbid obesity

Severe obesity is associated with a state of chronic inflammation. Sirtuins (SIRT) are a family of conserved enzymes which are able to affect many metabolic and inflammatory pathways thereby potentially improving health and increasing lifespan. We investigated the effect of weight loss on subcutaneous adipose tissue and liver mRNA and immunohistochemical expression of SIRT1, SIRT3, and SIRT6. Twenty-nine severely obese patients undergoing laparoscopic adjustable gastric banding (LAGB) were studied. Tissue samples were collected before and 6months after LAGB surgery. Tissue mRNA expression levels of SIRT1, SIRT3, and SIRT6 were correlated with clinical, biochemical, and histological parameters. In vitro, we studied sirtuin expression in native and stimulated monocytes, adipocytes, and hepatocytes. SIRT1, SIRT3, and SIRT6 mRNA expression was higher in the subcutaneous adipose tissue than in the liver. Weight loss resulted in a significant induction of SIRT1, SIRT3, and SIRT6 expression in the subcutaneous adipose tissue. In the liver, a significant increase after weight loss was observed, particularly for SIRT3 and SIRT6 mRNA expression; immunohistochemically, SIRT1 and SIRT3 expression was upregulated. Endotoxin and tumor necrosis factor-alpha suppressed SIRT1, SIRT3, and SIRT6 expression in human monocytes. The same stimuli suppressed total sirtuin deacetylase activity again, mainly in monocytes and less in adipocytes and hepatocytes. The relative abundance of adipose tissue mRNA expression of certain sirtuins exceeds its expression in the liver. Extensive weight loss increases sirtuin expression significantly both in adipose tissue and liver, probably as a consequence of reduced inflammation.

GW24-e3662 The comparative study on expression of SIRT1 signal transduction by Xuefuzhuyu capsule

ObjectivesThe Xuefuzhuyu capsule is used for the treatment of ischaemic heart disease in China. Evidences have demonstrated that Xuefuzhuyu capsule could protect cardiomyocytes from injury induced by ischaemia, but molecular...