Circulating endothelin-1 levels in obese patients with the metabolic syndrome

Ferri, Claudio; Bellini, Cesare; Desideri, Giovambattista; Baldoncini, R.; Properzi, Giuliana; Santucci, A.; Mattia, G. De

doi:10.1055/s-0029-1211794

Cited by 83 publications

(38 citation statements)

References 8 publications

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“…ET-1 stimulates leptin production and secretion in murine adipocytes (34) and circulating ET-1 levels are significantly higher in obese patients than in controls (8). In obese individuals, the cardiovascular system is highly infiltrated with adipose tissue.…”

Section: Discussionmentioning

confidence: 98%

Leptin increases endothelin type A receptor levels in vascular smooth muscle cells

Juan¹,

Chuang

Lien

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Leptin, one of the adipocytesecreted peptides, is involved in the control of appetite and body weight. Several studies have demonstrated that plasma leptin levels are elevated in obese subjects and are positively correlated with body weight. The arterial endothelin (ET) system plays an important role in the regulation of vascular tone, and ET-1 overexpression may be involved in the pathogenesis of the hypertension associated with insulin resistance. This study was performed to explore the regulatory effects of leptin on ET receptor expression and ET binding in A10 vascular smooth muscle cells (VSMCs) by use of Northern blotting, immunoblotting, and a 125 I-labeled ET-1 binding assay. The effect of leptin on ET receptor-mediated cell proliferation was also tested. The results showed that leptin caused a significant increase in [125 I]-ET-1 binding, which was time-and dose-dependent. Immunoblotting showed that expression of the ET type A receptor (ET AR) in leptin (10 Ϫ7 M)-treated cells was increased by up to 2.3-fold compared with controls. Levels of ET AR mRNA measured by Northern blotting were also increased by up to 2.2-fold in leptin (10 Ϫ7 M)-treated cells. Pretreatment with an ERK inhibitor, PD-98059 (2.5 ϫ 10 Ϫ5 M), blocked the leptin-induced increase in 125 I-ET-1 binding. Finally, ET-1 (10 Ϫ7 M)-stimulated cell proliferation was enhanced by leptin (10 Ϫ7 M) pretreatment, with a maximal increase of twofold compared with controls. In conclusion, leptin increases ET AR expression in VSMCs in a time-and dose-dependent manner. This effect is ERK dependent and is associated with increased ET-1-stimulated cell proliferation. These findings provide support for roles for leptin and the ET system in the pathogenesis of obesity-associated hypertension.endothelin-1; proliferation; leptin receptor; extracellular signal-regulated kinase

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Section: Discussionmentioning

confidence: 98%

Leptin increases endothelin type A receptor levels in vascular smooth muscle cells

Juan¹,

Chuang

Lien

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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“…Earlier studies have shown that circulatory levels of ET-1 are increased in obesity. 10,[20][21][22][23][24] We have recently shown that s.c. adipose tissue, which is the major adipose region, might contribute to the elevated levels of ET-1 in the obese state. 10 This study shows that the expression of ET-1 mRNA is higher in s.c. adipose tissue compared with OM adipose tissue, whereas ETR expression is similar in the two depots .…”

Section: Discussionmentioning

confidence: 99%

Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor

et al. 2008

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Objective: Levels of the vascular peptide endothelin-1 (ET-1) are significantly elevated in obesity. Adipose tissue-derived ET-1 attenuates insulin-mediated antilipolysis in human visceral adipocytes through the activation of the ET receptor B (ET B R), thereby linking ET-1 to insulin resistance. Whether ET-1 has direct effects on lipolysis in human adipocytes is not known. Research design and subjects: Endothelin-1 receptor (ETR) mRNA expression was determined by quatitative PCR in 130 nonobese and obese subjects. ET-1 mRNA in different adipose tissue regions was also assessed. ETR protein expression was analyzed by western blotting in 37 subjects. The effect of ET-1 on lipolysis was assessed in freshly isolated adipocytes and in vitro differentiated adipocytes from human donors. Results: Freshly isolated human adipocytes incubated with different concentrations of ET-1 showed no acute effect on lipolysis. In contrast, a 24 h incubation in primary cultures of human adipocytes resulted in a significant 50% increase in lipolysis. This effect was concentration dependent and could be mimicked by an agonist of the ET A receptor but not with a selective ET B R agonist. Adipocyte differentiation was not affected by any of the agonists. In subcutaneous (s.c.) adipose tissue from 19 nonobese and 18 obese subjects, the protein expression of ET A R was significantly higher in obese subjects whereas there was no difference in ET B R expression. Interestingly, the differences in protein expression were not observed at the mRNA level as ET A R expression was similar between lean and obese subjects. Conclusion: Long-term but not acute incubation of human adipocytes with ET-1 results in a significant increase in lipolysis. This appears to be mediated through the activation of ET A R, demonstrating a yet another receptor-specific effect of ET-1. In addition, the protein expression of ET A R is increased in s.c. adipose tissue in obesity, possibly through post-transcriptional mechanisms. An increased effect of ET-1 could be a mechanism that contributes to increased basal lipolysis in human obesity.

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“…Vasoconstriction to angiotensin-II is amplified in the obese animal (OZR), while reactivity to norepinephrine remains similar to the reactivity of the LZR; a similar pattern of reactivity has also been described in humans [81]. Metabolic syndrome patients have shown increased levels of endothelin-1 (ET-1), a potent vasoconstrictor, and an overall increase in response to vasoconstrictive agonists [82,83]. The profound impact mediated by prostanoid species and other metabolites of arachidonic acid on basal perfusion/resting vascular tone as well as on hyperemic responses has been well established [84][85][86][87].…”

Section: Vasoconstrictionmentioning

confidence: 94%

Obesity and vascular dysfunction

et al. 2008

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One of the most profound challenges facing public health and public health policy in Western society is the increased incidence and prevalence of both overweight and obesity. While this condition can have significant consequences for patient mortality and quality of life, it can be further exacerbated as overweight/obesity can be a powerful stimulus for the development of additional risk factors for a negative cardiovascular outcome, including increased insulin resistance, dyslipidemia and hypertension. This manuscript will present the effects of systemic obesity on broad issues of vascular function in both afflicted human populations and in the most relevant animal models. Among the topics that will be covered are alterations to vascular reactivity (both dilator and constrictor responses), adaptations in microvascular network and vessel wall structure, and alterations to the patterns of tissue/organ perfusion as a result of the progression of the obese condition. Additionally, special attention will be paid to the contribution of chronic inflammation as a contributor to alterations in vascular function, as well as the role of perivascular adipose tissue in terms of impacting vessel behavior. When taken together, it is clearly apparent that the development of the obese condition can have profound, and frequently difficult to predict, impacts on integrated vascular function. Much of this complexity appears to have its basis in the extent to which other co-morbidities associated with obesity (e.g., insulin resistance) are present and exert contributing effects.

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Circulating endothelin-1 levels in obese patients with the metabolic syndrome

Cited by 83 publications

References 8 publications

Leptin increases endothelin type A receptor levels in vascular smooth muscle cells

Leptin increases endothelin type A receptor levels in vascular smooth muscle cells

Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor

Obesity and vascular dysfunction

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