Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sоsnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

doi:10.1016/j.abb.2014.12.018

Cited by 50 publications

(40 citation statements)

References 46 publications

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“…Furthermore, knockout of Nox2 completely abolished aorta ROS production and restored IR expression and signaling in old age. The crucial role of metabolic disorder-induced Nox2 activation and oxidative damage of endothelial function was further demonstrated using an accelerated aging model of HFD-induced obesity and insulin resistance of mice at 12 m of age, which is equivalent to a human of ~50 years old when most metabolic and vascular diseases occur [1], [21], [23]. Once again we showed that inhibition of Nox2 activity using apocynin significantly reduced HFD-induced high blood pressure and aorta oxidative stress and preserved endothelial function.…”

Section: Discussionmentioning

confidence: 99%

Aging-associated metabolic disorder induces Nox2 activation and oxidative damage of endothelial function

Fan

Cahill-Smith

Geng

et al. 2017

Free Radical Biology and Medicine

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Oxidative stress attributable to the activation of a Nox2-containing NADPH oxidase is involved in the development of vascular diseases and in aging. However, the mechanism of Nox2 activation in normal aging remains unclear. In this study, we used age-matched wild-type (WT) and Nox2 knockout (KO) mice at 3–4 months (young); 11–12 months (middle-aged) and 21–22 months (aging) to investigate age-related metabolic disorders, Nox2 activation and endothelial dysfunction. Compared to young mice, middle-aged and aging WT mice had significant hyperglycaemia, hyperinsulinaemia, increased systemic oxidative stress and higher blood pressure. Endothelium-dependent vessel relaxation to acetylcholine was significantly impaired in WT aging aortas, and this was accompanied by increased Nox2 and ICAM-1 expressions, MAPK activation and decreased insulin receptor expression and signaling. However, these aging-associated disorders were significantly reduced or absent in Nox2KO aging mice. The effect of metabolic disorder on Nox2 activation and endothelial dysfunction was further confirmed using high-fat diet-induced obesity and insulin resistance in middle-aged WT mice treated with apocynin (a Nox2 inhibitor). In vitro experiments showed that in response to high glucose plus high insulin challenge, WT coronary microvascular endothelial cells increased significantly the levels of Nox2 expression, activation of stress signaling pathways and the cells were senescent, e.g. increased p53 and β–galactosidase activity. However, these changes were absent in Nox2KO cells. In conclusion, Nox2 activation in response to aging-associated hyperglycaemia and hyperinsulinaemia plays a key role in the oxidative damage of vascular function. Inhibition or knockout of Nox2 preserves endothelial function and improves global metabolism in old age.

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Section: Discussionmentioning

confidence: 99%

Aging-associated metabolic disorder induces Nox2 activation and oxidative damage of endothelial function

Fan

Cahill-Smith

Geng

et al. 2017

Free Radical Biology and Medicine

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“…However, only R + W increased plasma nitrite levels; R + W also produced a greater decrease in MDA. These variables are markers of morbidity and mortality in many populations (Yucel et al ., ; Zhang et al ., ), so combining walking with resistance exercise may have additional benefits, thus warranting a recommendation that patients with PAD should perform both types of exercise in the same training session. Physicians, coaches and instructors should encourage patients with PAD to integrate combined walking and resistance exercise into their daily activities as the combination has an acute beneficial impact on oxidative stress, as well as producing improvements in walking capacity and muscle function.…”

Section: Discussionmentioning

confidence: 99%

Acute effects of walking and combined exercise on oxidative stress and vascular function in peripheral artery disease

Andrade-Lima

Correia

Germano-Soares

et al. 2016

Clin Physio Funct Imaging

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The aim of this study was to compare the effects of a single session of walking and combined exercise on oxidative stress and vascular function in peripheral arterial disease patients. Thirteen patients with peripheral arterial disease underwent two experimental sessions in random order: walking (ten sets of 2-min walking at the speed corresponding to the onset of claudication pain with 2-min interval between sets) and combined exercise (1 × 10 reps in eight resistance exercises plus five-two-minute sets of walking). Before and after the exercise, vascular function (blood flow, leg vascular resistance and blood-flow postreactive hyperaemia) and oxidative stress (malondialdehyde and plasma nitrite levels) were obtained. Blood flow increased similarly after both sessions, whilst leg vascular resistance decreased similarly after both sessions. Plasma nitrite increased only after the combined exercise. Malondialdehyde decreased after both sessions, and the decrease was greater after combined exercise. As a conclusion, a single session of combined exercise improves blood flow and leg vascular resistance similarly to walking session; however, combined exercise promoted better effects on oxidative stress.

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“…H. gordonii is among the most popular anti-obesity products on the market [26]. Obesity is a chronic disease and amongst other morbidities, it is associated with an increase in oxidative stress [27]. The role of oxidative stress in the pathogenesis of various ailments, such as psychiatric, inflammatory and infectious diseases has been well documented [6, 9, 12, 28].…”

Section: Discussionmentioning

confidence: 99%

In vitro anti-HIV and antioxidant activity of Hoodia gordonii (Apocynaceae), a commercial plant product

Kapewangolo

Knott

Shithigona

et al. 2016

BMC Complement Altern Med

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Background Hoodia gordonii products are widely commercialized for anti-obesity purposes; however, minimal research is available on the other health properties demonstrated by this popular herbal plant.Methods H. gordonii crude extracts (ethanol and ethyl acetate) were assayed for in vitro anti-HIV-1 protease (PR), reverse transcriptase (RT) and integrase activity. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power assays were used for the antioxidant analysis. In addition, qualitative and quantitative phytochemical analyses of the extracts were determined using standard methods.Results H. gordonii extract demonstrated good inhibition against HIV RT with IC50 values of 73.55 ± 0.04 and 69.81 ± 9.45 μg/mL for ethanol and ethyl acetate extracts, respectively. Both extracts also demonstrated inhibitory activity against HIV PR with IC50 values of 97.29 ± 0.01 and 63.76 ± 9.01 μg/mL for ethanol and ethyl acetate extracts. In addition, H. gordonii also showed good antioxidant activity with IC50 values of 124.6 ± 11.3 and 126.2 ± 3.15 μg/mL obtained for ethanol and ethyl acetate extracts, respectively. The reducing power of H. gordonii extracts increased as the concentration increased which confirmed the presence of antioxidants (reductants) in the extracts. Phytochemical screening of H. gordonii revealed the presence of phenolics, alkaloids, terpenes, steroids, cardiac glycosides and tannins in the ethanolic extract, while the ethyl acetate extract only showed the presence of phenolics, cardiac glycosides and steroids. The total phenolic content was 420 ± 0.17 and 319.9 ± 0.2 mg GAE/g for the ethanol and ethyl acetate extracts, respectively. The ethanol extract, which revealed the presence of tannins, had a tannin content of 330 ± 0.2 mg TAE/g extract.ConclusionThis data suggests that H. gordonii has good in vitro inhibition against selected HIV-1 enzymes as well as antioxidant properties, suggesting new potential uses for this commercial plant.

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Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

Cited by 50 publications

References 46 publications

Aging-associated metabolic disorder induces Nox2 activation and oxidative damage of endothelial function

Aging-associated metabolic disorder induces Nox2 activation and oxidative damage of endothelial function

Acute effects of walking and combined exercise on oxidative stress and vascular function in peripheral artery disease

In vitro anti-HIV and antioxidant activity of Hoodia gordonii (Apocynaceae), a commercial plant product

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