Treatment with n-3 polyunsaturated fatty acids reverses endothelial dysfunction and oxidative stress in experimental menopause

Cappellari, Gianluca Gortan; Losurdo, Pasquale; Mazzucco, Sara; Panizon, Emiliano; Jevnicar, Mitja; Macaluso, L.; Fabris, Bruno; Barazzoni, Rocco; Biolo, Gianni; Carretta, Renzo; Zanetti, Michela

doi:10.1016/j.jnutbio.2012.07.012

Cited by 53 publications

(59 citation statements)

References 49 publications

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“…Oestrogen affects tissue PUFA content 56 and the capacity of adipose tissue to uptake and store fatty acids in TG-enriched lipid droplets 57 . In postmenopausal women, PUFA intake improved endothelial function 27 and physical performance 58 . Fatty acids also play a role in ageing; small-to-medium-chain saturated fatty acids were inversely associated with telomere length in postmenopausal women in a recent study 59 .…”

Section: Discussionmentioning

confidence: 98%

“…Menopause-associated oestrogen depletion has several wellestablished metabolic consequences. Menopause promotes atherosclerosis through changes in lipid profile, endothelial dysfunction and oxidative stress 26,27 . Hormonal changes in menopause promote higher body fat, in particular abdominal obesity, contributing to the increased CVD and metabolic risk 28,29 .…”

Section: Discussionmentioning

confidence: 99%

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A metabolic view on menopause and ageing

et al. 2014

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The ageing of the global population calls for a better understanding of age-related metabolic consequences. Here we report the effects of age, sex and menopause on serum metabolites in 26,065 individuals of Northern European ancestry. Age-specific metabolic fingerprints differ significantly by gender and, in females, a substantial atherogenic shift overlapping the time of menopausal transition is observed. In meta-analysis of 10,083 women, menopause status associates with amino acids glutamine, tyrosine and isoleucine, along with serum cholesterol measures and atherogenic lipoproteins. Among 3,204 women aged 40-55 years, menopause status associates additionally with glycine and total, monounsaturated, and omega-7 and -9 fatty acids. Our findings suggest that, in addition to lipid alterations, menopause may contribute to future metabolic and cardiovascular risk via influencing aminoacid concentrations, adding to the growing evidence of the importance of amino acids in metabolic disease progression. These observations shed light on the metabolic consequences of ageing, gender and menopause at the population level.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

A metabolic view on menopause and ageing

et al. 2014

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“…Plasma glucose and nonesterified fatty acid (NEFA) levels were determined by standard enzymatic colorimetric assays (21,22).…”

Section: Plasma Insulin and Nonesterified Fatty Acidsmentioning

confidence: 99%

“…Commercial kits were used to measure catalase (Amplex Red Catalase Assay Kit; Invitrogen) and glutathione peroxidase activities (Abcam, Cambridge, U.K.). Western blots were performed as previously described (21,22,25). Equal loading was checked by Ponceau S staining and GAPDH reprobing.…”

Section: Glutathione and Antioxidant Enzyme Activitiesmentioning

confidence: 99%

Unacylated Ghrelin Reduces Skeletal Muscle Reactive Oxygen Species Generation and Inflammation and Prevents High-Fat Diet–Induced Hyperglycemia and Whole-Body Insulin Resistance in Rodents

et al. 2016

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Excess reactive oxygen species (ROS) generation and inflammation may contribute to obesity-associated skeletal muscle insulin resistance. Ghrelin is a gastric hormone whose unacylated form (UnAG) is associated with whole-body insulin sensitivity in humans and may reduce oxidative stress in nonmuscle cells in vitro. We hypothesized that UnAG 1) lowers muscle ROS production and inflammation and enhances tissue insulin action in lean rats and 2) prevents muscle metabolic alterations and normalizes insulin resistance and hyperglycemia in high-fat diet (HFD)-induced obesity. In 12-week-old lean rats, UnAG (4-day, twice-daily subcutaneous 200-mg injections) reduced gastrocnemius mitochondrial ROS generation and inflammatory cytokines while enhancing AKT-dependent signaling and insulinstimulated glucose uptake. In HFD-treated mice, chronic UnAG overexpression prevented obesity-associated hyperglycemia and whole-body insulin resistance (insulin tolerance test) as well as muscle oxidative stress, inflammation, and altered insulin signaling. In myotubes, UnAG consistently lowered mitochondrial ROS production and enhanced insulin signaling, whereas UnAG effects were prevented by small interfering RNA-mediated silencing of the autophagy mediator ATG5. Thus, UnAG lowers mitochondrial ROS production and inflammation while enhancing insulin action in rodent skeletal muscle. In HFDinduced obesity, these effects prevent hyperglycemia and insulin resistance. Stimulated muscle autophagy could contribute to UnAG activities. These findings support UnAG as a therapeutic strategy for obesity-associated metabolic alterations.Clustered metabolic abnormalities, including excess reactive oxygen species (ROS) generation and inflammation activation, are proposed contributors to the onset of skeletal muscle insulin resistance (1-5). Excess muscle ROS production and inflammation are indeed linked at the level of inhibitor of kB (IkB)/nuclear factor-kB (NF-kB) activation and may cause insulin resistance by inhibiting insulin signaling downstream of insulin receptor (2,3,5). Ghrelin is a peptide hormone predominantly secreted by the stomach, and its acylated form (AG) is a major hypothalamic orexigenic signal (6,7). Sustained AG administration causes weight gain and hyperglycemia despite enhanced muscle mitochondrial oxidative capacity (8,9) by increasing food intake, hepatic gluconeogenesis, and fat deposition in rodents (10,11). A comprehensive understanding of the metabolic impact of ghrelin, however, has recently been allowed by reports of independent, more favorable effects of its unacylated form (UnAG). Although no specific UnAG receptor has yet been identified, UnAG counteracts glucogenic effects of AG as well as

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“…10) Ovarian steroid deprivation can induce oxidative stress in various tissues including myocardium. 11,12) Moreover, administration of estrogens attenuates the generation of reactive oxygen species (ROS) and reduces apoptosis by anti-oxidative stress following ischemia/reoxygen in myocardium. 13,14) Hydrogen sulfide (H 2 S), a newly characterized gasotransmitter, has recently been shown to have cardioprotective effects.…”

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confidence: 99%

Exercise Increases Cystathionine-<i>γ</i>-lyase Expression and Decreases the Status of Oxidative Stress in Myocardium of Ovariectomized Rats

et al. 2016

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SummaryExercise could be a therapeutic approach for cardiovascular dysfunction induced by estrogen deficiency. Our previous study has shown that estrogen maintains cystathionine-γ-lyase (CSE) expression and inhibits oxidative stress in the myocardium of female rats. In the present study, we investigated whether exercise improves CSE expression and oxidative stress status and ameliorates isoproterenol (ISO)-induced cardiac damage in ovariectomized (OVX) rats. The results showed that treadmill training restored the ovariectomy-induced reduction of CSE and estrogen receptor (ER)α and decrease of total antioxidant capacity (T-AOC) and increase of malondialdehyde (MDA). The level of CSE was positively correlated to T-AOC and ERα while inversely correlated to MDA. OVX rats showed increases in the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) and the percentage of TUNEL staining in myocardium upon ISO insult compared to sham rats. Exercise training significantly reduced the serum levels of LDH and CK and the percentage of TUNEL staining in myocardium upon ISO insult in OVX rats. In cultured cardiomyocytes, ISO treatment decreased cell viability and increased LDH release, while overexpression of CSE increased cell viability and decreased LDH release in the cells upon ISO insult. The results suggest that exercise training improves the oxidative stress status and ameliorates the cardiac damage induced by oxidative stress in OVX rats. The improvement of oxidative stress status by exercise might be at least partially due to upregulation of CSE/H 2 S signaling. (Int Heart J 2016; 57: 96-103) Key words: Hydrogen sulfide, Estrogens, Estrogen receptor M enopause is a risk factor for many cardiovascular diseases. Cross-sectional data show that the incidence of cardiovascular diseases is much higher in post-menopausal women compared with women of the same age who are pre-menopausal. 1,2) Many studies in animal models have demonstrated that a lack of ovary hormones, in particular estrogens, has detrimental effects on various organs including the cardiovascular system.3) Hormone replacement therapy (HRT) has therefore been recommended to postmenopausal women. However, the controversies regarding the safety of HRT have drawn attention to new therapies for postmenopausal women. 4,5) Exercise training is one of the therapies used to prevent postmenopausal syndrome. Numerous epidemiological studies have convincingly shown that physical exercise has a beneficial effect on cardiovascular disease outcomes. Exercise reduces heart rate and blood pressure, augments myocardial oxygen uptake, and regulates circulating blood volume as well as various metabolic processes.6,7) Furthermore, it has been shown that postmenopausal women who engage in intermittent, moderate-intensity physical training have a decreased risk of cardiovascular complications. 8,9) Oxidative stress is considered one of the main causative factors in various cardiovascular disorders including postmenopausal cardiovascular disorders.10) Ovarian stero...

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Treatment with n-3 polyunsaturated fatty acids reverses endothelial dysfunction and oxidative stress in experimental menopause

Cited by 53 publications

References 49 publications

A metabolic view on menopause and ageing

A metabolic view on menopause and ageing

Unacylated Ghrelin Reduces Skeletal Muscle Reactive Oxygen Species Generation and Inflammation and Prevents High-Fat Diet–Induced Hyperglycemia and Whole-Body Insulin Resistance in Rodents

Exercise Increases Cystathionine-<i>γ</i>-lyase Expression and Decreases the Status of Oxidative Stress in Myocardium of Ovariectomized Rats

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