Resistance to acute NO-mimetic and EDHF-mimetic effects of leptin in the metabolic syndrome

Bełtowski, Jerzy; Wójcicka, Grażyna; Jamróz-Wiśniewska, Anna; Marciniak, Andrzej

doi:10.1016/j.lfs.2009.08.002

Cited by 26 publications

(35 citation statements)

References 53 publications

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“…Data are the mean±SEM. Intra-group statistical differences were analyzed by the Kruskal-Wallis test followed by Mann-Whitney's U test; *P<0.05 vs. control group; † †P<0.01 vs. pair-fed group to blood pressure homeostasis inducing a pressor response attributable to central sympathoactivation [23] and a depressor response attributable to the vasodilation of conduit and resistance vessels [24]. Due to the leptin receptor missense mutation, obese (fa/fa) Zucker rats showed an impairment of sympathetic baroreceptor reflexes as well as an impaired vasodilatory response due to a defective intracellular Ca 2+ handling and proliferation in vascular smooth muscle cells, leading to the adult-onset hypertension [25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Sleeve Gastrectomy Reduces Blood Pressure in Obese (fa/fa) Zucker Rats

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Sleeve Gastrectomy Reduces Blood Pressure in Obese (fa/fa) Zucker Rats

et al. 2011

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“…This concept requires further validation because the vasodilatory actions of leptin in other vascular beds have been found to be inconsistent [28, 29]. In high-calorie fed obese rats, however, recent studies by Beltowski et al have indicated that acutely infused leptin was associated with a hypertensive effect related, at least in part, to impaired vascular NO and EDHF production characteristic of obesity [30]. …”

Section: Leptin Sympathetic Nervous System and The Regulation Ofmentioning

confidence: 99%

“…From these findings, the concept of “ selective leptin resistance ” as a mechanism for the development of hypertension in obesity has emerged [31, 32]. The precise factors behind this selectivity are yet to be fully defined [32, 34], but may involve alterations in the SOCS3 signaling pathway or IRS-1 (insulin receptor substrate-1) serine residue phosphorylation [30, 35, 36]. …”

Section: Chronic Hyperleptinemia Leptin Resistance and Hypertensionmentioning

confidence: 99%

Obesity Hypertension: The Regulatory Role of Leptin

Kshatriya

Liu

Salah

et al. 2011

International Journal of Hypertension

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Leptin is a 16-kDa-peptide hormone that is primarily synthesized and secreted by adipose tissue. One of the major actions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake and elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect mechanisms, may play an important role in cardiovascular and renal regulation. While the relevance of endogenous leptin needs further clarification, it appears to function as a pressure and volume-regulating factor under conditions of health. However, in abnormal situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for direct renal, vascular, and cardiac damage.

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“…Leptin infusion also caused vasodilatation of the brachial artery [10] and coronary artery [11] in non-obese, healthy human subjects. Nonetheless, in pathological conditions such as obesity or metabolic syndrome (MetS), resistance to leptin’s vasodilatory effect has been observed in both animal [12-14] and human studies [15,16]. Obesity and hyperleptinemia caused by diet lead to impaired leptin-induced NO and cyclic guanosine monophosphate production in the aortic wall of rats [12] and in aortic endothelial cells of mice [13].…”

Section: Introductionmentioning

confidence: 99%

Leptin is associated with vascular endothelial function in overweight patients with type 2 diabetes

Morioka¹,

Emoto²,

Yamazaki³

et al. 2014

Cardiovasc Diabetol

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BackgroundThe adipocyte-derived hormone leptin plays a key role in the regulation of appetite and body weight. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-related atherosclerosis and cardiovascular disease. In this study, we investigated the association of plasma leptin levels with vascular endothelial function in lean and overweight patients with type 2 diabetes.MethodsOne hundred seventy-one type 2 diabetic patients, of which 85 were overweight (body mass index (BMI) ≥ 25 kg/m2), were enrolled in this cross-sectional study. Plasma leptin concentrations were measured by enzyme-linked immunosorbent assay. Flow-mediated dilatation (FMD) of the brachial artery was measured to evaluate vascular endothelial function using ultrasound.ResultsNo significant difference in FMD was found between the lean and overweight groups (7.0 ± 3.8% and 6.5 ± 3.6%, respectively; p = 0.354). FMD was negatively correlated with age (r = −0.371, p < 0.001) and serum creatinine levels (r = −0.236, p = 0.030), but positively correlated with BMI (r = 0.330, p = 0.002) and plasma leptin levels (r = 0.290, p = 0.007) in the overweight group. FMD was not associated with any parameters in the lean group. Multiple regression analysis including possible atherosclerotic risk factors revealed that the plasma leptin level (β = 0.427, p = 0.013) was independently associated with FMD in the overweight group (R2 = 0.310, p = 0.025), but not the lean group.ConclusionPlasma leptin levels are associated with vascular endothelial function in overweight patients with type 2 diabetes.

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Resistance to acute NO-mimetic and EDHF-mimetic effects of leptin in the metabolic syndrome

Cited by 26 publications

References 53 publications

Sleeve Gastrectomy Reduces Blood Pressure in Obese (fa/fa) Zucker Rats

Sleeve Gastrectomy Reduces Blood Pressure in Obese (fa/fa) Zucker Rats

Obesity Hypertension: The Regulatory Role of Leptin

Leptin is associated with vascular endothelial function in overweight patients with type 2 diabetes

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