Prevention of concentric hypertrophy and diastolic impairment in aortic-banded rats treated with resveratrol

This study was designed to examine the effects of the antioxidant resveratrol on cardiac structure and function in pressure overload (PO)-induced cardiac hypertrophy. Male Sprague-Dawley rats were subjected to sham operation and the aortic banding procedure. A subgroup of sham control and aortic-banded rats were treated with resveratrol for 2 wk after surgery. Echocardiographic analysis of cardiac structure and function along with Western blot analysis of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and redox factor-1 (ref-1) were performed in all groups after 4 wk of surgery. Banded rats showed significantly increased left ventricle-to-body weight ratio. Echocardiographic analysis showed that the interventricular septal wall thickness and left ventricular posterior wall thickness at systole and diastole were significantly increased in banded rats. Also, a significant increase in isovolumic relaxation time was observed in banded rats. Measured eNOS, iNOS, and ref-1 protein levels were significantly reduced in banded rats. Resveratrol treatment prevented the above changes in cardiac structure, function, and protein expression in banded rats. Aortic banding after 4 wk resulted in concentric remodeling and impaired contractile function due to PO on the heart. The 2-wk treatment with resveratrol was found to abolish PO-induced cardiac hypertrophy. Resveratrol may therefore be beneficial against PO-induced cardiac hypertrophy found in clinical settings of hypertension and aortic valve stenosis.     

Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans

Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here, we treated 11 healthy, obese men with placebo and 150?mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30?days. Resveratrol significantly reduced sleeping and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels, increased citrate synthase activity without change in mitochondrial content, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30?days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction.     

Focus: The Science of Stress: Resveratrol Supplants Captopril’s Protective Effect on Cardiac Remodeling in a Hypertension Model Elicited by Renal Artery Stenosis

Background: Renovascular hypertension elicits cardiac damage and remodeling. Two-kidney, one-clip (2K1C) is an experimental model used to study hypertension pathophysiology. In this model, the renin-angiotensin-system (RAS) is overactive due to renal artery stenosis, leading to cardiac remodeling. Redox mechanisms underlying RAS activation mediate hypertension-induced cardiovascular damage. Preclinical studies and clinical trials demonstrated resveratrol’s protective effects in cardiovascular diseases, mainly attributed to its antioxidant properties. We hypothesized resveratrol alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor would be beneficial against cardiac damage caused by renovascular hypertension. Objective: We investigated the benefits of resveratrol against cardiac remodeling in 2K1C rats compared with captopril. Methods: Male Wistar rats underwent unilateral renal stenosis – 2K1C Goldblatt model of hypertension. Systolic Blood Pressure (SBP) was measured before and 6 weeks after surgery. Hypertensive 2K1C rats presented SBP≥160 mmHg. From the 6^th week after the surgery, the animals received oral resveratrol (20 mg/kg), captopril (12 mg/kg), or their combination for 3 times per week for 3 weeks. Whole heart hypertrophy was evaluated. Histological assays assessed left ventricle hypertrophy and fibrosis. Results: Renovascular hypertension caused cardiac hypertrophy, accompanied by increased myocyte diameter and collagen deposition. Resveratrol reduced 2K1C rats’ SBP and whole heart hypertrophy, independently of captopril. Resveratrol caused a higher reduction in ventricular hypertrophy than captopril. Collagen deposition was greater reduced by 2K1C treated only with resveratrol than with captopril alone or combined with resveratrol. Conclusion: Independent of captopril, resveratrol prompts cardioprotective effects on cardiomyocyte remodeling and fibrosis resulting from renovascular hypertension in 2K1C rats.     

Emerging role of SIRT3 in endothelial metabolism,angiogenesis, and cardiovascular disease

Sirtuin 3 (SIRT3) a mitochondrial enzyme that plays an important role in energy homeostasis, cardiac remodeling, and heart failure (HF). The expression of SIRT3 declines with advanced age, cardiovascular, and metabolic diseases. Accumulating evidence suggests that SIRT3 plays a critical role in protecting the heart from cardiac hypertrophy, cardiac dysfunction associated with HF, and in the protection of cardiac cells from stress-mediated cell death. Clinical studies have demonstrated that HF with preserved ejection fraction (HFpEF) in patients present with abnormalities in coronary microcirculation related to endothelial dysfunction and coronary microvascular rarefaction. Although SIRT3-mediated regulation of mitochondrial homeostasis and heart function has been intensively investigated, the effect of SIRT3 on endothelial cell (EC) glycolytic metabolism and microvascular function has not been well studied. ECs utilize glycolysis for generating ATP rather than oxidative phosphorylation to maintain their normal functions and promote angiogenesis and EC–cardiomyocyte interactions. Emerging evidence indicates that SIRT3 is involved in the regulation of endothelial metabolism and angiogenesis and thus affects the development of cardiovascular diseases associated with aging. This review will discuss the current knowledge of SIRT3 and its functional role on endothelial metabolism, cardiac function, and cardiovascular diseases.     

Resveratrol and the mitochondria: From triggering the intrinsic apoptotic pathway to inducing mitochondrial biogenesis,a mechanistic view

BackgroundMitochondria, the power plants of the cell, are known as a cross-road of different cellular signaling pathways. These cytoplasmic double-membraned organelles play a pivotal role in energy metabolism and regulate calcium flux in the cells. It is well known that mitochondrial dysfunction is associated with different diseases such as neurodegeneration and cancer. A growing body of literature has shown that polyphenolic compounds exert direct effects on mitochondrial ultra-structure and function. Resveratrol is known as one of the most common bioactive constituents of red wine, which improves mitochondrial functions under in vitro and in vivo conditions.Scope of reviewThis paper aims to review the molecular pathways underlying the beneficial effects of resveratrol on mitochondrial structure and functions. In addition, we discuss the chemistry and main sources of resveratrol.Major conclusionsResveratrol represents the promising effects on mitochondria in different experimental models. However, there are several reports on the detrimental effects elicited by resveratrol on mitochondria.General significanceAn understanding of the chemistry and source of resveratrol, its bioavailability and the promising effects on mitochondria brings a new hope to therapy of mitochondrial dysfunction-related diseases.     

Resveratrol Protects SAMP8 Brain Under Metabolic Stress: Focus on Mitochondrial Function and Wnt Pathway

Metabolic stress induced by high-fat (HF) diet leads to cognitive dysfunction and aging, but the physiological mechanisms are not fully understood. Senescence-accelerated prone mouse (SAMP8) models were conducted under metabolic stress conditions by feeding HF for 15 weeks, and the preventive effect of resveratrol was studied. This dietary strategy demonstrates cognitive impairment in SAMP8-HF and significant preventive effect by resveratrol-treated animals. Hippocampal changes in the proteins involved in mitochondrial dynamics optic atrophy-1 protein (OPA1) and mitofusin 2 (MFN2) comprised a differential feature found in SAMP8-HF that was prevented by resveratrol. Electronic microscopy showed a larger mitochondria in SAMP8-HF + resveratrol (SAMP8-HF + RV) than in SAMP8-HF, indicating increases in fusion processes in resveratrol-treated mice. According to the mitochondrial morphology, significant increases in the I-NDUFB8, II-SDNB, III-UQCRC2, and V-ATPase complexes, in addition to that of voltage-dependent anion channel 1 (VDAC1)/porin, were found in resveratrol-treated animals with regard to SAMP8-HF, reaching control-animal levels. Moreover, tumor necrosis factor alpha (TNF-α) and interleukin (IL-6) were increased after HF, and resveratrol prevents its increase. Moreover, we found that the HF diet affected the Wnt pathway, as demonstrated by β-catenin inactivation and modification in the expression of several components of this pathway. Resveratrol induced strong activation of β-catenin. The metabolic stress rendered in the cognitive and cellular pathways altered in SAMP8 focus on different targets in order to act on preventing cognitive impairment in neurodegeneration, and resveratrol can offer therapeutic possibilities for preventive strategies in aging or neurodegenerative conditions.     

白藜芦醇对力竭训练动物能量代谢和抗氧化功能的影响

白藜芦醇具有多种生物学功能和药用价值,例如抗炎、抗衰老、抗病毒、抗肿瘤等。为了探讨白藜芦醇在外源性抗氧化剂方面的开发价值。本研究建立了跑步力竭SD大鼠模型,应用不同浓度的白藜芦醇处理大鼠4周。研究显示,白藜芦醇处理可以剂量依赖性方式提高大鼠的跑步力竭时间(p<0.05)。白藜芦醇处理以剂量依赖方式降低大鼠血清乳酸和尿素氮水平并升高游离脂肪酸水平(p<0.05)。白藜芦醇处理以剂量依赖方式升高大鼠体内超氧化物歧化酶和过氧化氢酶水平,并降低丙二醛水平(p<0.05)。白藜芦醇处理以剂量依赖方式降低血清肌酸激酶、天冬氨酸转氨酶和丙氨酸转氨酶水平(p<0.05)。此外,白藜芦醇明显减轻了大鼠骨骼肌的病理改变。因此,白藜芦醇可提高跑步力竭大鼠的抗疲劳能力,改善能量代谢方式,提高机体抗氧化能力,减少运动损伤。     

Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes

Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function.     

Treatment with low-dose resveratrol reverses cardiac impairment in obese prone but not in obese resistant rats

We hypothesized that a low-dose resveratrol will reverse cardiovascular abnormalities in rats fed a high-fat (HF) diet. Obese prone (OP) and obese resistant (OR) rats were fed an HF diet for 17 weeks; Sprague-Dawley rats fed laboratory chow served as control animals. During the last 5 weeks of study, treatment group received resveratrol daily by oral gavage at a dosage of 2.5 mg/kg body weight. Assessments included echocardiography, blood pressure, adiposity, glycemia, insulinemia, lipidemia, and inflammatory and oxidative stress markers. Body weight and adiposity were significantly higher in OP rats when compared to OR rats. Echocardiographic measurements showed prolonged isovolumic relaxation time in HF-fed OP and OR rats. Treatment with resveratrol significantly improved diastolic function in OP but not in OR rats without affecting adiposity. OP and OR rats had increased blood pressure which remained unchanged with treatment. OP rats had elevated fasting serum glucose and insulin, whereas OR rats had increased serum glucose and normal insulin concentrations. Resveratrol treatment significantly reduced serum glucose while increasing serum insulin in both OP and OR rats. Inflammatory and oxidative stress markers, serum triglycerides and low-density lipoprotein were higher in OP rats, which were significantly reduced with treatment. In conclusion, HF induced cardiac dysfunction in both OP and OR rats. Treatment reversed abnormalities in diastolic heart function associated with HF feeding in OP rats, but not in OR rats. The beneficial effects of resveratrol may be mediated through regression of hyperglycemia, oxidative stress and inflammation.     

Resveratrol ameliorates metabolic disorders and muscle wasting in streptozotocin-induced diabetic rats

Diabetes mellitus (DM) is characterized by dysregulated energy metabolism. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in diabetic animals. However, its overall in vivo effects on energy metabolism and the underlying mechanism require further investigation. In the present study, electrospray ionization-tandem mass spectrometry was employed to characterize the urine and plasma metabolomes of control, streptozotocin-induced DM and RSV-treated DM rats. Using principal component analysis (PCA) and heat map analysis, we discovered significant differences among control and experimental groups. RSV treatment significantly reduced the metabolic abnormalities in DM rats. Compared with the age-matched control rats, the level of carnitine was lower, and the levels of acetylcarnitine and butyrylcarnitine were higher in the urine and plasma of DM rats. RSV treatment ameliorated the deranged carnitine metabolism in DM rats. In addition, RSV treatment attenuated the diabetic ketoacidosis and muscle protein degradation, as evidenced from the attenuation of elevated urinary methyl-histidine and plasma branched-chain amino acids levels in DM rats. The beneficial effects of RSV in DM rats were correlated with activation of hepatic AMP-activated protein kinase and SIRT1 expression, increase of hepatic and muscular mitochondrial biogenesis and inhibition of muscle NF-κB activities. We concluded that RSV possesses multiple beneficial metabolic effects in insulin-deficient DM rats, particularly in improving energy metabolism and reducing protein wasting.     

Protective effect of peptide semax (ACTH(4-7)Pro-Gly-Pro) on the rat heart rate after myocardial infarction

Semax, a member of ACTH-derived peptides family, was used in treatment of ischemic stroke in patients. It decreased neurological deficiency and reduced NO hyperproduction in the rat brain caused by acute cerebral hypoperfusion. We suggest that semax is also capable of protecting the rat heart from ischemic damage 28 days after myocardial infarction (MI) induced by left descendent coronary artery occlusion. Semax (150 microg/kg) was given i. p. in the operating day twice: 15 min and 2 hours after coronary occlusion, and once a day for the following 6 days. In 28 days after infarction, the MI group developed cardiac hypertrophy, cell growth was caused mainly by the increase of contractile filaments not supported by the appropriate mitochondrial growth that indicated an impaired energy supply of the cells. Moreover, cardiac hypertrophy was accompanied by decreased mean arterial blood pressure and cardiac contractile function and increased left ventricular end-diastolic pressure. Pharmacological change of cardiac afterload revealed that, in 28 days after MI, the rat heart was not able to change its contractile performance in response to either increase or decrease of systemic blood pressure, and as a result could not maintain its diastolic pressure. All these changes obviously reflect development of heart failure. Semax did not affect cardiac work but partially prevented end-diastolic pressure growth in left ventricle as well as ameliorated cardiomyocyte hypertrophy and disproportionate growth of contractile and mitochondrial apparatus, thus exerting beneficial effect on the left ventricular remodeling and heart failure development late after myocardial infarction.     

Decreased cardiac mitochondrial NADP+-isocitrate dehydrogenase activity and expression: a marker of oxidative stress in hypertrophy development

Mitochondrial dysfunction subsequent to increased oxidative stress and alterations in energy metabolism is considered to play a role in the development of cardiac hypertrophy and its progression to failure, although the sequence of events remains to be elucidated. This study aimed at characterizing the impact of hypertrophy development on the activity and expression of mitochondrial NADP+-isocitrate dehydrogenase (mNADP+-ICDH), a metabolic enzyme that controls redox and energy status. We expanded on our previous finding of its inactivation through posttranslational modification by the lipid peroxidation product 4-hydroxynonenal (HNE) in 7-wk-old spontaneously hypertensive rat (SHR) hearts before hypertrophy development (Benderdour et al. J Biol Chem 278: 45154-45159, 2003). In this study, we used 7-, 15-, and 30-wk-old SHR and Sprague-Dawley (SD) rats with abdominal aortic coarctation. Compared with age-matched control Wistar-Kyoto (WKY) rats, SHR hearts showed a significant 25% decrease of mNADP+-ICDH activity, which preceded in time 1) the decline in its protein and mRNA expression levels (between 10% and 35%) and 2) the increase in hypertrophy markers. The chronic and persistent loss of mNADP+-ICDH activity in SHR was associated with enhanced tissue accumulation of HNE-mNADP+-ICDH and total HNE-protein adducts at all ages and contrasted with the profile of changes in the activity of other mitochondrial enzymes involved in antioxidant or energy metabolism. Two-way ANOVA of the data also revealed a significant effect of age on most parameters measured in SHR and WKY hearts. The mNADP+-ICDH activity, protein, and mRNA expression were reduced between 25% and 35% in coarctated SD rats and were normalized by treatment of SHR or coarctated SD rats with renin-angiotensin system inhibitors, which prevented or attenuated hypertrophy. Altogether, our data show that cardiac mNADP+-ICDH activity and expression are differentially and sequentially affected in hypertrophy development and, to a lesser extent, with aging. Decreased cardiac mNADP+-ICDH activity, which is attributed at least in part to HNE adduct formation, appears to be a relevant early and persistent marker of mitochondrial oxidative stress-related alterations in hypertrophy development. Potentially, this could also contribute to the aetiology of cardiomyopathy.     

Carvedilol Prevents Ovariectomy-Induced Myocardial Contractile Dysfunction in Female Rat

Carvedilol has beneficial effects on cardiac function in patients with heart failure but its effect on ovariectomy-induced myocardial contractile dysfunction remains unclear. Estrogen deficiency induces myocardial contractile dysfunction and increases cardiovascular disease risk in postmenopausal women. Our aim was to investigate whether carvedilol, a beta receptor blocker, would prevent ovariectomy-induced myocardial contractile dysfunction. Female rats (8 weeks old) that underwent bilateral ovariectomy were randomly assigned to receive daily treatment with carvedilol (OVX+CAR, 20 mg/kg), placebo (OVX) and SHAM for 58 days. Left ventricle papillary muscle was mounted for isometric tension recordings. The inotropic response to Ca²⁺ (0.62 to 3.75 mM) and isoproterenol (Iso 10⁻⁸ to 10⁻² M) were assessed. Expression of calcium handling proteins was measured by western blot analysis. Carvedilol treatment in the OVX animals: prevented weight gain and slight hypertrophy, restored the reduced positive inotropic responses to Ca²⁺ and isoproterenol, prevented the reduction in SERCA2a expression, abolished the increase in superoxide anion production, normalized the increase in p22^phox expression, and decreased serum angiotensin converting enzyme (ACE) activity. This study demonstrated that myocardial contractile dysfunction and SERCA2a down regulation were prevented by carvedilol treatment. Superoxide anion production and NADPH oxidase seem to be involved in this response.     

Resveratrol enhances fatty acid oxidation capacity and reduces resistin and Retinol-Binding Protein 4 expression in white adipocytes

Resveratrol is a naturally occurring polyphenol known to affect energy metabolism and insulin sensitivity in mice and lipogenic gene expression in adipocytes. Here, we sought to get further insight into the impact of resveratrol on adipocyte biology by studying its effects on oxidative metabolism and the expression of the insulin resistance-related adipokines resistin and Retinol-Binding Protein 4 (RBP4) in mature adipocytes. Effects were assessed in 3T3-L1 adipocytes and in adipocytes derived from primary mouse embryonic fibroblasts (MEF). Besides reducing triacylglycerol content and the mRNA levels of lipogenic genes, resveratrol treatment resulted in both models in increased mRNA levels of carnitine palmitoyltransferase 1 (a rate-limiting enzyme in mitochondrial fatty acid oxidation), reduced mRNA levels of receptor interacting protein 140 (a suppressor of oxidative metabolism), and signs of enhanced flux through the fatty acid beta-oxidation pathway. In primary MEF-derived adipocytes, the treatment also increased mitochondrial DNA content and the mRNA levels of subunit II of cytochrome oxidase (a component of the mitochondrial respiratory chain) and of uncoupling protein 1. Expression of resistin and RBP4 was reduced in both adipocyte models following resveratrol treatment. The results indicate that resveratrol directly acts in mature white adipocytes to favor a remodeling toward increased oxidative capacity and reduced lipogenesis, while down-regulating two putative insulin resistance factors. These results constitute novel insights into resveratrol action in adipocytes that add to the potential of this food phytochemical and its synthetic analogues for the control of obesity and related metabolic disorders.     

Abnormal cardiac energetics in patients carrying the A3243G mtDNA mutation measured in vivo using phosphorus MR spectroscopy

Cardiomyopathy is a frequent cause of morbidity and mortality in patients carrying the A3243G transition in the mitochondrial DNA (mtDNA) tRNALeu(UUR) gene, the most common heteroplasmic single mtDNA defect. We used phosphorus magnetic resonance spectroscopy (31P-MRS) to look for evidence of an in vivo bioenergetics defect in patients carrying the A3243G mtDNA mutation with and without echocardiographic signs of left ventricle hypertrophy (LVH). Eight patients, three with LVH, carrying the A3243G mtDNA mutation and 10 healthy subjects underwent one-dimensional chemical shift imaging 31P-MRS. In the patients, mean cardiac phosphocreatine to adenosine triphosphate ratio (PCr/ATP) (1.55 +/- 0.58) was significantly reduced compared to the control group (2.34 +/- 0.14; P < 0.001). Cardiac PCr/ATP was within the normal range only in one case that showed normal echocardiography. Our results point to a central role of bioenergetics deficit in the development of cardiac hypertrophy in patients with the A3243G mtDNA mutation. Impaired cardiac energy metabolism in patients with normal echocardiography suggests that the enhancement of mitochondrial function may be beneficial not only to patients with cardiac hypertrophy but also to those patients carrying the mutation in the absence of signs of cardiac hypertrophy and/or dysfunction but with cardiac bioenergetics deficit.     

Resveratrol treatment improves the altered metabolism and related dysbiosis of gut programed by prenatal high-fat diet and postnatal high-fat diet exposure

A maternal high-fat (HF) diet sensitizes offspring to the adverse effects of postnatal HF intake and can lead to metabolic dysregulation. Resveratrol, a natural polyphenolic compound found in grapes and red wine, could help to relieve metabolic syndrome dysregulation. Since the gut microbiota is known to be closely related to metabolic homeostasis, this study aimed to investigate the impact of a combination of maternal and postweaning HF diets on the gut microbiota and whether resveratrol could relieve the gut dysbiosis associated with metabolic dysregulation. Sprague–Dawley dams were sustained on either a chow or HF diet before mating, during pregnancy and during lactation. Their offspring were randomly fed chow or a HF diet after weaning. Four experimental groups were generated: CC (maternal/postnatal chow diet), HC (maternal HF/postnatal chow diet), CH (maternal chow/postnatal high-fat diet) and HH (maternal/postnatal HF diet). A fifth group consisted of HH with resveratrol treatment. We found that both maternal and postnatal HF exposure has a distinct effect on the gut microbiota metagenome of offspring. Maternal HF diet exposure decreased plasma acetate, propionate and butyrate level, while postnatal HF diet exposure decreased plasma acetate level in adult life. The metabolic dysregulation programed by the maternal and postnatal HF diets was related to the relevant gut microbiota. Resveratrol treatment ameliorated the altered plasma propionate level related to maternal HF and postnatal HF diet treatment. Resveratrol treatment also improved most of the altered metabolic dysregulation and related dysbiosis programmed by maternal and postnatal HF diet exposure.     

Resveratrol treatment increases mitochondrial biogenesis and improves viability of porcine germinal-vesicle stage vitrified-warmed oocytes

Vitrification induces mitochondrial dysfunction in warmed oocytes, and degeneration and biogenesis of mitochondria are crucial for maintaining oocyte quality. The present study addresses a hypothesis that treatment of vitrified-warmed oocytes with resveratrol could improve the viability of oocytes by activating mitochondrial biosynthesis. Cumulus oocyte complexes (COCs) collected from gilt ovaries were vitrified, warmed, and cultured in a medium containing vehicle or 1 μM resveratrol. Resveratrol treatment improved survival, maturation, and mitochondrial membrane potential of vitrified-warmed oocytes, but did not improve the development into blastocysts after parthenogenetic activation. Resveratrol treatment increased mitochondrial synthesis, as determined by the expression levels of TOMM20 and mitochondrial DNA copy number, in vitrified-warmed oocytes, but not in non-vitrified oocytes. In addition, the effect of resveratrol treatment on mitochondrial synthesis was reduced by EX527, a SIRT1 inhibitor. Resveratrol treatment of vitrified-warmed oocytes increased the expression levels of genes involved in mitochondrial synthesis (TFAM, POLG, and PGC1α) and increased nuclear translocation of NRF2. Furthermore, vitrification induced mitophagy, as confirmed by a reduction in TOMM20 expression and decreased p62 aggregation, whereas resveratrol treatment did not affect these mitophagic features. In conclusion, vitrification induced mitochondrial clearance in oocytes, whereas activation of SIRT1 by resveratrol treatment facilitated the recovery of vitrified-warmed oocytes through the activation of mitochondrial synthesis.