Resveratrol and SRT1720 Elicit Differential Effects in Metabolic Organs and Modulate Systemic Parameters Independently of Skeletal Muscle Peroxisome Proliferator-activated Receptor γ Co-activator 1α (PGC-1α)

Svensson, Kristoffer; Schnyder, Svenia; Albert, Verena; Cardel, Bettina; Quagliata, Luca; Terracciano, Luigi; Handschin, Christoph

doi:10.1074/jbc.m114.590653

Cited by 22 publications

(27 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Fig. 1C, AMPK activation occurred 1–6 h after treatment but had subsided by 24 h. Svensson et al (2015)) also reported that SRT1720 does not activate AMPK in C2C12 myotubes. However, Svensson et al visualized p-AMPK 24 h after treatment and therefore may have missed earlier activation.…”

Section: Resultssupporting

confidence: 53%

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

Park

Ahmad

et al. 2017

EBioMedicine

View full text Add to dashboard Cite

The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK), an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE) in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1.

show abstract

Section: Resultssupporting

confidence: 53%

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

Park

Ahmad

et al. 2017

EBioMedicine

View full text Add to dashboard Cite

show abstract

“…Lagouge et al (2006) verified that RSV's effects were related with an induction of oxidative phosphorylation and mitochondrial biogenesis genes and these effects were largely explained by an RSV-mediated an increase in PGC-1a activity (Lagouge et al, 2006). On the contrary, Svensson et al (2015) have reported that the beneficial effects of RSV on energy expenditure occur even in the absence of PGC-1a (Svensson et al, 2015). Intriguingly, Higashida et al (2013) showed that overexpression of SIRT1 decreased PGC-1a coactivator activity (Higashida et al, 2013).…”

Section: Discussionmentioning

confidence: 64%

High glucose and free fatty acids induce endothelial progenitor cell senescence via PGC‐1α/SIRT1 signaling pathway

Song

Yang

Qiu

et al. 2017

Cell Biology International

View full text Add to dashboard Cite

The objective of the research was to investigate the function of endothelial progenitor cells (EPCs) in the conditions of high glucose and lipids, which has been widely used to mimic the metabolic disorder that occurs in type 2 diabetic mellitus, and further to verify the role of PGC-1α and SIRT1, cellular energy metabolism regulators, in the process of senescence of EPCs with these combined stimuli. Circulating EPCs were incubated in absence or presence of high glucose (25 mM), FFA (200 µM) or both. EPCs senescence was assessed by β-galactosidase staining, EPCs telomerase activity was measured by telomeric repeat ampli-fication protocol assay, in vitro angiogenesis assay and MTT assays were performed to assess angiogenesis and proliferation ability of EPCs. The results showed that combined stimuli inhibited EPCs reendothelialization ability in vitro, accelerated EPCs senescence and decreased the telomerase activity. Meanwhile, with combined stimuli, the expression of PGC-1α increased whereas SIRT1 expression decreased in EPCs accompanied by activation of P53/P21 signaling pathway. Conversely, transfection of EPCs with PGC-1α-siRNA rescued EPCs premature senescence and up-regulated SIRT1 and decreased P53/P21 expression, correlating closely with the down-regulation of PGC-1α itself. In addition, the combined stimuli induced up-regulation of PGC-1α expression was partly mediated by ROS and P38 signaling pathway. Overall, the data presented here identify PGC-1α as a potent negative regulator of EPCs' senescence under combined stimuli, which is partly mediated by SIRT1/P53/P21 signaling pathway.

show abstract

“…), long‐term (13 week) RSV treatment has been reported to increase insulin signaling in this tissue (Svensson et al. ). Conversely, treating 3T3‐L1 adipocytes with a high dose of RSV (50 μmol/L) has been shown to induce insulin resistance (Wang et al.…”

Section: Discussionmentioning

confidence: 97%

“…The improvements in whole-body glucose homeostasis following COM treatment were mirrored by increases in insulin-stimulated AKT phosphorylation in scAT and to a lesser extent triceps muscle. Although MET is not thought to increase adipose tissue insulin action (Ciaraldi et al 2002), long-term (13 week) RSV treatment has been reported to increase insulin signaling in this tissue (Svensson et al 2015). Conversely, treating 3T3-L1 adipocytes with a high dose of RSV (50 lmol/L) has been shown to induce insulin resistance (Wang et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of combined resveratrol and metformin therapy in treating diet‐induced insulin resistance

Frendo‐Cumbo

MacPherson

Wright

2016

Physiological Reports

View full text Add to dashboard Cite

The polyphenol compound resveratrol (RSV) has attracted attention due to its reputed beneficial effects on insulin sensitivity. Our lab has previously identified protective effects of RSV against the development of type 2 diabetes in rats. These effects occurred in a manner similar to thiazolidinedione's (TZDs), a class of insulin sensitizing drugs. TZDs are commonly prescribed in combination with metformin (MET) and thus we sought to examine the combined effects of RSV and MET in treating insulin resistance. Male C57BL6 mice were fed a low‐ (LFD; 10% Kcal from fat) or high‐fat diet (HFD; 60% Kcal from fat) for 9 weeks to induce glucose and insulin intolerance. HFD mice were then assigned to control (HFD), MET (231.28 ± 12.24 mg/kg/day), RSV (93.68 ± 3.51 mg/kg/day), or combined (COM; MET 232.01 ± 17.12 mg/kg/day and RSV 92.77 ± 6.92 mg/kg/day) treatment groups. Changes in glucose and insulin tolerance and tissue‐specific insulin signaling were measured 4 weeks post‐treatment. RSV or MET alone did not have beneficial effects on glucose tolerance, although MET significantly improved insulin tolerance compared to HFD. Glucose and insulin tolerance were significantly improved in COM compared to HFD and this was mirrored by enhanced insulin‐stimulated AKT phosphorylation in triceps muscle and inguinal subcutaneous adipose tissue in COM compared to HFD mice. Improvements with COM treatment were not explained by differences in body weight, adiposity, or markers of adipose tissue inflammation. In summary, this study provides evidence of beneficial effects of combined RSV and MET therapy in treating impairments in glucose homeostasis.

show abstract

Resveratrol and SRT1720 Elicit Differential Effects in Metabolic Organs and Modulate Systemic Parameters Independently of Skeletal Muscle Peroxisome Proliferator-activated Receptor γ Co-activator 1α (PGC-1α)

Cited by 22 publications

References 49 publications

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

High glucose and free fatty acids induce endothelial progenitor cell senescence via PGC‐1α/SIRT1 signaling pathway

Beneficial effects of combined resveratrol and metformin therapy in treating diet‐induced insulin resistance

Contact Info

Product

Resources

About