Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner
Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany. American Journal of Clinical Nutrition
(Impact Factor: 6.77).
07/2010; 92(1):5-15. DOI: 10.3945/ajcn.2009.28435
Caloric restriction leads to retardation of the aging processes and to longer life in many organisms. This effect of caloric restriction can be mimicked by resveratrol, a natural plant product present in grapes and red wine, which is known as a potent activator of sirtuin 1 [silent mating type information regulation 2 homolog 1 (Sirt1)].
One main effect of caloric restriction in mammals is a reduction of body fat from white adipose tissue. We sought to identify the effects of resveratrol on fat cell biology and to elucidate whether Sirt1 is involved in resveratrol-mediated changes.
Human Simpson-Golabi-Behmel syndrome preadipocytes and adipocytes were used to study proliferation, adipogenic differentiation, glucose uptake, de novo lipogenesis, and adipokine secretion. Sirt1-deficient human preadipocytes were generated by using a lentiviral small hairpin RNA system to study the role of Sirt1 in resveratrol-mediated changes.
Resveratrol inhibited preadipocyte proliferation and adipogenic differentiation in a Sirt1-dependent manner. In human adipocytes, resveratrol stimulated basal and insulin-stimulated glucose uptake. De novo lipogenesis was inhibited in parallel with a down-regulation of lipogenic gene expression. Furthermore, resveratrol down-regulated the expression and secretion of interleukin-6 and interleukin-8. Sirt1 was only partially responsible for the regulation of resveratrol-mediated changes in adipokine secretion.
Taken together, our data suggest that resveratrol influences adipose tissue mass and function in a way that may positively interfere with the development of obesity-related comorbidities. Thus, our findings open up the new perspective that resveratrol-induced intracellular pathways could be a target for prevention or treatment of obesity-associated endocrine and metabolic adverse effects.
Available from: Gabriel Davidov-Pardo
- "Resveratrol has also been shown to inhibit certain types of cancer, which has been attributed to its ability to induce apoptosis, activate caspase, modulate signaling pathways, decrease cell proliferation, arrest cell cycles, and decrease metastasis (Murtaza et al., 2013). Resveratrol have proven useful in the management of obesity through its ability to decrease lipid synthesis, increase lipolysis, and reduce lipid accumulation (Alves, 2012; Fischer-Posovszky et al., 2010; Picard et al., 2004). In primates, resveratrol was found to reduce body weight gain by increasing satiety and resting metabolic rate, as well as inhibiting torpor expression (Dal-Pan, Blanc, & Aujard, 2010). "
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ABSTRACT: Resveratrol is a polyphenol from the stilbens family that has been reported to have various benefits for human health, including antioxidant, anti-inflammatory, anti-carcinogenic, anti-obesity, and heart/brain protective effects. However, the utilization of resveratrol as a nutraceutical in the food industry is currently limited due to its poor water-solubility, high chemical instability, and low oral bioavailability. Encapsulation of resveratrol can be used to improve its water-dispersibility, chemical stability, and bioavailability. This paper reviews delivery systems available to encapsulate, protect and release resveratrol, and highlights their potential applications within the food industry.
Trends in Food Science & Technology 08/2014; 38(2). DOI:10.1016/j.tifs.2014.05.003 · 4.65 Impact Factor
Available from: Yanwen Wang
- "Furthermore, (silent mating type information regulation 2, homolog) 1 (Sirt1) is an NAD-dependent deacetylase that also serves as a master metabolic sensor, regulated by NAD+ concentration, and modulates cellular energy metabolism . Sirt1 has been reported to inhibit adipogenesis in 3T3-L1 cells by repressing PPARγ
 and is involved in the regulation of the number and function of adipocytes . Therefore, the present study was conducted to determine the effect of UA on adipogenesis and mechanism of action, with the primary focus on the regulation of UA on the energy sensors AMPK and Sirt1 and further their downstream lipogenic targets in 3T3-L1 adipocytes. "
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ABSTRACT: Ursolic acid (UA) is a triterpenoid compound with multiple biological functions. This compound has recently been reported to possess an anti-obesity effect; however, the mechanisms are less understood.
As adipogenesis plays a critical role in obesity, the present study was conducted to investigate the effect of UA on adipogenesis and mechanisms of action in 3T3-L1 preadipocytes.
The 3T3-L1 preadipocytes were induced to differentiate in the presence or absence of UA for 6 days. The cells were determined for proliferation, differentiation, fat accumulation as well as the protein expressions of molecular targets that regulate or are involved in fatty acid synthesis and oxidation. The results demonstrated that ursolic acid at concentrations ranging from 2.5 µM to 10 µM dose-dependently attenuated adipogenesis, accompanied by reduced protein expression of CCAAT element binding protein β (C/EBPβ), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT element binding protein α (C/EBPα) and sterol regulatory element binding protein 1c (SREBP-1c), respectively. Ursolic acid increased the phosphorylation of acetyl-CoA carboxylase (ACC) and protein expression of carnitine palmitoyltransferase 1 (CPT1), but decreased protein expression of fatty acid synthase (FAS) and fatty acid-binding protein 4 (FABP4). Ursolic acid increased the phosphorylation of AMP-activated protein kinase (AMPK) and protein expression of (silent mating type information regulation 2, homolog) 1 (Sirt1). Further studies demonstrated that the anti-adipogenic effect of UA was reversed by the AMPK siRNA, but not by the Sirt1 inhibitor nicotinamide. Liver kinase B1 (LKB1), the upstream kinase of AMPK, was upregulated by UA. When LKB1 was silenced with siRNA or the inhibitor radicicol, the effect of UA on AMPK activation was diminished.
Ursolic acid inhibited 3T3-L1 preadipocyte differentiation and adipogenesis through the LKB1/AMPK pathway. There is potential to develop UA into a therapeutic agent for the prevention or treatment of obesity.
PLoS ONE 07/2013; 8(7):e70135. DOI:10.1371/journal.pone.0070135 · 3.23 Impact Factor
Available from: Thomas Kietzmann
- "Resveratrol has been shown to modulate several key signaling molecules in adipocytes, including Sirt1 [50, 51], AMPK [52–54], and PI3K/Akt [52, 55–57]. To examine whether Sirt1, AMPK, and/or PI3K are involved in the resveratrol-dependent downregulation of PAI-1 gene expression, we used specific inhibitors of these signaling pathways as well as knockout cells. "
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ABSTRACT: Increased plasminogen activator inhibitor-1 (PAI-1) levels are associated with a number of pathophysiological complications; among them is obesity. Resveratrol was proposed to improve obesity-related health problems, but the effect of resveratrol on PAI-1 gene expression in obesity is not completely understood. In this study, we used SGBS adipocytes and a model of human adipose tissue inflammation to examine the effects of resveratrol on the production of PAI-1. Treatment of SGBS adipocytes with resveratrol reduced PAI-1 mRNA and protein in a time- and concentration-dependent manner. Further experiments showed that obesity-associated inflammatory conditions lead to the upregulation of PAI-1 gene expression which was antagonized by resveratrol. Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions. Instead, we demonstrate that the resveratrol effects on PAI-1 induction under inflammatory conditions were mediated via inhibition of the NF κ B pathway. Together, resveratrol can act as NF κ B inhibitor in adipocytes and thus the subsequently reduced PAI-1 expression in inflamed adipose tissue might provide a new insight towards novel treatment options of obesity.
Oxidative Medicine and Cellular Longevity 06/2013; 2013(4):793525. DOI:10.1155/2013/793525 · 3.36 Impact Factor
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