Is leptin involved in phagocytic NADPH oxidase overactivity in obesity? Potential clinical implications

Fortuño, Ana; Bidegain, Julen; Baltanás, Ana; Moreno, María U.; Montero, Laura; Landecho, Manuel F.; Beloqui, Óscar; Dı́ez, Javier; Zalba, Guillermo

doi:10.1097/hjh.0b013e32833c21af

Cited by 45 publications

(34 citation statements)

References 33 publications

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“…Fortuno and colleagues demonstrated that phagocytic NADPH oxidase activity was increased in obese subjects ( P < 0.05) and was related to preclinical atherosclerosis in this condition [17]. Also animal studies have provided interesting results of diet-induced obesity on the NADPH oxidases activity and expression of its subunits.…”

Section: Discussionmentioning

confidence: 99%

The −930A>G polymorphism of the CYBA gene is associated with premature coronary artery disease. A case–control study and gene–risk factors interactions

et al. 2014

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Reactive oxygen species (ROS) are involved in the pathogenesis of atherosclerosis and coronary artery disease (CAD). NADPH oxidases are the main source of ROS in the vasculature. p22phox is a critical component of vascular NADPH oxidases and is encoded by the CYBA (cytochrome b245 alpha) gene. The −930A>G CYBA polymorphism (rs9932581:A>G) modulates the activity of the CYBA promoter, and influences CYBA transcriptional activity. The aim of the present study was to analyze a possible association between the −930A>G polymorphism and CAD and to search for gene–traditional risk factors interactions. 480 subjects were studied: 240 patients with premature CAD, 240 age and sex matched blood donors. The −930A>G polymorphism was genotyped using the TaqMan® Pre-designed SNP Genotyping Assay (Applied Biosystems). The −930G allele carrier state was a risk factor for CAD (OR 2.03, 95 % CI 1.21–3.44, P = 0.007). A synergistic effect of the −930G allele with overweight/obesity (BMI ≥ 25) and cigarette smoking was found. The estimated CAD risk for BMI ≥ 25 and the −930G allele interaction was about 160 % greater than that predicted by assuming additivity of the effects, and about 40 % greater for interaction of cigarette smoking and the −930G allele. Overweight/obesity was a risk factor for CAD only in the −930G allele carriers (P < 10−10) but not in the AA homozygotes (P = 1.00). In conclusion the −930A>G CYBA polymorphism is associated with CAD in the Polish population. The −930G allele carriers are particularly at risk of consequences of obesity and tobacco smoke exposure.

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Section: Discussionmentioning

confidence: 99%

The −930A>G polymorphism of the CYBA gene is associated with premature coronary artery disease. A case–control study and gene–risk factors interactions

et al. 2014

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“…This effect, however, appears to be lost after prolonged treatment, and in ob/ob mice, leptin reduces markers of oxidative stress. 32 Moreover, although a correlation between the plasma level of leptin and NOX activity in human monocytes was reported, 43 in an experimental model, leptin, different from angiotensin II, does not induce the NADPH oxidase. 29 Moreover, when we determined the effect of leptin on the angiotensin II-induced H 2 O 2 formation of angiotensin II type 1 receptor expressing HUVECs, we observed that leptin completely blocked the angiotensin II-induced reactive oxygen species formation (K. Schröder, 2012, unpublished observation), giving rise to the possibility that the beneficial effect of in vivo leptin on angiotensin II-induced hypertension and endothelial dysfunction are, in part, mediated by NADPH oxidase inhibition.…”

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confidence: 99%

Leptin Potentiates Endothelium-Dependent Relaxation by Inducing Endothelial Expression of Neuronal NO Synthase

Benkhoff

Loot

Pierson

et al. 2012

ATVB

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Objective— Obesity is associated with hyperleptinemia but it is not clear whether leptin protects vascular function or promotes dysfunction. We therefore studied the consequences of hyperleptinemia in lean mice. Methods and Results— Wild-type and endothelial NO synthase (eNOS) −/− mice were infused with leptin (0.4 mg/kg per day, 7 days), and endothelium-dependent relaxation was studied in aortic segments. Leptin had no effect on acetylcholine-induced endothelium-dependent relaxation in normal wild-type mice but restored endothelium-dependent relaxation in wild-type mice treated with angiotensin II (0.7 mg/kg per day, 7 days) to induce endothelial dysfunction. Leptin also sensitized aortae from eNOS −/− mice to acetylcholine, an effect blocked by neuronal NOS (nNOS) inhibition and not observed in eNOS-nNOS double −/− mice. Consistent with these findings, leptin induced nNOS expression in murine and human vessels and human endothelial but not smooth muscle cells. Aortic nNOS expression was also induced in mice by a high-fat diet. Mechanistically, leptin increased endothelial Janus kinase 2 and signal transducer and activator of transcription 3 phosphorylation, and inhibition of Janus kinase 2 prevented nNOS induction in cultured cells and leptin-induced relaxations in eNOS −/− mice. Conclusion— Leptin induces endothelial nNOS expression, which compensates, in part, for a lack of NO production by eNOS to maintain endothelium-dependent relaxation.

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“…66 The hormone leptin activates NOX and induces the production of reactive intermediates such as H 2 O 2 and hydroxyl radical. 67 In a rodent model, leptin injection caused higher levels of plasma and urinary lipid hydroperoxide, MDA, isoprostane, and protein carbonyl content compared to levels seen in nontreated controls. 68 In addition, leptin also stimulates the proliferation of monocytes and macrophages and thus promotes the production of proinflammatory cytokines.…”

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Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

Manna

Jain

2015

Metabolic Syndrome and Related Disorders

858

541

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Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk factors, and potential strategies to regulate body weight loss/gain for better health benefits.

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Is leptin involved in phagocytic NADPH oxidase overactivity in obesity? Potential clinical implications

Abstract: These findings show that phagocytic NADPH oxidase activity is increased in obesity and is related to preclinical atherosclerosis in this condition. We also suggest that hyperleptinemia may contribute to phagocytic NADPH oxidase overactivity in obesity.

Cited by 45 publications

References 33 publications

The −930A>G polymorphism of the CYBA gene is associated with premature coronary artery disease. A case–control study and gene–risk factors interactions

The −930A>G polymorphism of the CYBA gene is associated with premature coronary artery disease. A case–control study and gene–risk factors interactions

Leptin Potentiates Endothelium-Dependent Relaxation by Inducing Endothelial Expression of Neuronal NO Synthase

Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

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