Leptin Effect on Endothelial Nitric Oxide Is Mediated Through Akt–Endothelial Nitric Oxide Synthase Phosphorylation Pathway

Vecchione, Carmine; Maffei, Angelo; Colella, Salvatore; Aretini, Alessandra; Poulet, Roberta; Frati, Giacomo; Gentile, Maria Teresa; Fratta, Luigi; Trimarco, Valentina; Trimarcö, Bruno; Lembo, Giuseppe

doi:10.2337/diabetes.51.1.168

Cited by 296 publications

(242 citation statements)

References 36 publications

(39 reference statements)

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“…Indeed, the multiplicity of leptin's involvement in vascular physiology, ranging from vasodilation through upregulation of nitric oxide biosynthesis 7 to promoting atherosclerosis through multiple mechanisms in a leptin-resistant state, 6,41 makes it difficult to isolate the direct effects of leptin. This was a selected target population; therefore, results cannot be extrapolated to other population groups.…”

Section: Discussionmentioning

confidence: 99%

“…6 Leptin has both beneficial and detrimental effects on the cardiovascular system. On the one hand, it induces vasodilation by promoting nitric oxide release in the endothelium, 7 but on the other hand, leptin increases sympathetic nerve activity 6 and promotes the release of vasoconstrictive substances, 8 which could contribute to obesity-related hypertension. Furthermore, leptin also increases the production of damaging reactive oxygen species (ROS) 9 and the secretion of inflammatory markers, 10,11 which contribute to atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

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Carotid cross-sectional wall area is significantly associated with serum leptin levels, independent of body mass index: the SABPA study

et al. 2012

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Hypertension and obesity are serious health burdens in sub-Saharan Africa. Urbanized Africans seem to be more susceptible to the development of these diseases than Caucasians. Current research suggests that leptin may be an important contributor to the development of hypertension and atherosclerosis. The aim of this study was to investigate leptin levels and their associations with cardiovascular function in urbanized Africans and Caucasians. Serum leptin, ambulatory blood pressure and carotid intima-media thickness were measured, and the cross-sectional wall area (CSWA) was calculated. The results showed that Africans had higher leptin levels (Po0.001), ambulatory blood pressure (Po0.001), carotid intima-media thickness (Po0.01) and CSWA (Po0.01) than Caucasians. As we found no interaction between ethnicity and gender for the association between leptin and the cardiovascular variables, we focused mainly on the total group of Africans and Caucasians. In single, partial and multiple regression analyses, positive associations of ambulatory systolic blood pressure (b ¼ 0.256; Po0.001), diastolic blood pressure (b ¼ 0.143; P ¼ 0.012), pulse pressure (b ¼ 0.327; Po0.001) and CSWA (b ¼ 0.107; P ¼ 0.038) with leptin were observed. Even after adjusting for body mass index (BMI), the association between CSWA (b ¼ 0.107; P ¼ 0.038) and leptin remained. Our findings therefore suggest that leptin may contribute to the development of atherosclerosis, independent of BMI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Carotid cross-sectional wall area is significantly associated with serum leptin levels, independent of body mass index: the SABPA study

et al. 2012

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“…Moreover, leptin hormone is able to directly activate NO production in vessels and this activation is dependent on endothelium integrity 30 . Thus, the hyperinsulinemia and hyperleptinemia observed in high-fat diet animals could be partially responsible for the increased endothelial NO production and/or release in the vasculature of obese rats.…”

Section: Time (Min)mentioning

confidence: 99%

Alterações vasculares em ratos obesos por dieta rica em gordura: papel da Via L-arginina/NO Endotelial

Nascimento¹,

Baptista²,

Pereira³

et al. 2011

Arq. Bras. Cardiol.

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“…As expected, the adipocyte-derived hormone leptin was also elevated in obese subjects in the present study. Leptin increases endothelial expression of nitric oxide and causes vasodilatation in vitro and in animal models [Fruhbeck, 1999;Vecchione et al, 2002].…”

Section: Two Previous Studies By Egan Et Al Demonstrated Increased Fomentioning

confidence: 99%

Sympathetic Vascular Tone in Human Obesity

Agapitov

Sinkey

Dopp

et al. 2004

Journal of Hypertension

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Obesity is associated with increased sympathoactivation that elevates arterial pressure. However, the mechanism linking sympathetic activation to arterial pressure is unclear. Specifically, it has never been demonstrated unequivocally that sympathetically mediated vasoconstriction is increased in obesity. This project tested the hypothesis that sympathetic vascular tone is increased in obese normotensive and hypertensive subjects.The effect of weight loss on sympathetic vascular tone was also assessed.Sympathetic vascular tone was assessed as forearm vasodilatation to intra-arterial phentolamine (α 1/2 -adrenergic receptor antagonist). Pharmacological responses were correlated with skeletal muscle sympathetic nerve activity (mSNA). Obese subjects with and without hypertension had increased mSNA. However, the vasodilatator response to phentolamine was not augmented in obese normotensive and hypertensive subjects versus lean controls. Additionally, weight loss did not alter phentolamine's vasodilatator response, despite reducing mSNA and arterial pressure in obese groups. These results indicate that sympathetic vascular tone is not increased in obesity despite higher mSNA.These studies also assessed forearm resistance vessel function using intra-arterial nitroprusside (nitric oxide donor) and isoproterenol (β 2 -adrenergic receptor agonist). The effects of weight loss on these responses were studied in the obese groups. The response to both vasodilators was blunted, but only in obese hypertensive subjects. Weight loss normalized the response to nitroprusside but not to isoproterenol. This result suggests that obesity-related hypertension is associated with vascular smooth muscle dysfunction, which can be improved by weight loss. Blunted vasodilatation to isoproterenol suggests an abnormality on β 2 -adrenergic receptor-dependent mechanisms that may or may not depend on the endothelium. Also, mental stress-induced forearm vasodilatation was blunted in obese normotensive subjects, which was not normalized by weight loss. 2In conclusion, increased sympathetic nerve activity does not augment forearm sympathetic vascular tone. This dissociation could be due to opposing local factors (e.g. insulin, leptin) or to a different target of limb sympathoactivation (e.g. adipocytes vs. vascular). Sympathetic drive to tissues other than the peripheral circulation may play a more important role in arterial pressure elevation in obesity, either directly or indirectly.Abstract Approved: ____________________________________ Thesis Supervisor ____________________________________

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Leptin Effect on Endothelial Nitric Oxide Is Mediated Through Akt–Endothelial Nitric Oxide Synthase Phosphorylation Pathway

Cited by 296 publications

References 36 publications

Carotid cross-sectional wall area is significantly associated with serum leptin levels, independent of body mass index: the SABPA study

Carotid cross-sectional wall area is significantly associated with serum leptin levels, independent of body mass index: the SABPA study

Alterações vasculares em ratos obesos por dieta rica em gordura: papel da Via L-arginina/NO Endotelial

Sympathetic Vascular Tone in Human Obesity

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