Preserved endothelial function in human obesity in the absence of insulin resistance

Assar, Mariam El; Adana, Juan Carlos Ruíz de; Angulo, Javier; Martínez, María Luz Pindado; Matías, Alberto Hernández; Rodríguez‐Mañas, Leocadio

doi:10.1186/1479-5876-11-263

Cited by 40 publications

(34 citation statements)

References 41 publications

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“…However, the question remains: Is loss of NO production somehow due to excess adiposity, or is its etiology derived from those conditions commonly associated with obesity? Interestingly, endothelial dysfunction was found to occur in morbidly obese humans only when insulin resistance was present [248]. And, severely obese humans, in the absence of insulin resistance, showed better flow-mediated dilation compared with normal and obese insulin-sensitive subjects [249].…”

Section: No Bioavailability Is Diminished In Obese and Diabetic Stmentioning

confidence: 99%

Regulation of obesity and insulin resistance by nitric oxide

Sansbury

Hill

2014

Free Radical Biology and Medicine

220

193

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Obesity is a risk factor for developing type 2 diabetes and cardiovascular disease and has quickly become a world-wide pandemic with few tangible and safe treatment options. While it is generally accepted that the primary cause of obesity is energy imbalance, i.e., the calories consumed are greater than are utilized, understanding how caloric balance is regulated has proven a challenge. Many “distal” causes of obesity, such as the structural environment, occupation, and social influences, are exceedingly difficult to change or manipulate. Hence, molecular processes and pathways more proximal to the origins of obesity—those that directly regulate energy metabolism or caloric intake—appear to be more feasible targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of diet-induced obesity and in obese and insulin resistant patients, and increasing NO output has remarkable effects on obesity and insulin resistance. This review discusses the role of NO in regulating adiposity and insulin sensitivity and places its modes of action into context with the known causes and consequences of metabolic disease.

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Section: No Bioavailability Is Diminished In Obese and Diabetic Stmentioning

confidence: 99%

Regulation of obesity and insulin resistance by nitric oxide

Sansbury

Hill

2014

Free Radical Biology and Medicine

220

193

View full text Add to dashboard Cite

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“…Interestingly, the vasodilatory response to bradykinin was weaker in the insulin-resistant group compared with the non-insulin-resistant group despite similar serum adiponectin levels in the two groups [48] supporting the lack of influence of adiponectin circulating levels on vascular function.…”

Section: Discussionmentioning

confidence: 73%

“…El Assar et al [48] investigated endothelium-dependent relaxation to bradykinin in human mesenteric arteries in obese individuals with and without insulin resistance. Interestingly, the vasodilatory response to bradykinin was weaker in the insulin-resistant group compared with the non-insulin-resistant group despite similar serum adiponectin levels in the two groups [48] supporting the lack of influence of adiponectin circulating levels on vascular function.…”

Section: Discussionmentioning

confidence: 99%

Similar Adiponectin Levels in Obese Normotensive and Obese Hypertensive Men and No Vasorelaxant Effect of Adiponectin on Human Arteries

Dreier

Asferg

Berg

et al. 2015

Basic Clin Pharma Tox

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Obesity is a strong risk factor for hypertension, but the mechanism linking obesity to hypertension is not fully elucidated. In obesity, circulating concentrations of adiponectin are decreased and hypoadiponectinaemia has in some but not all studies been associated with increased risk of hypertension. Due to this inconsistency, we decided to study adiponectin from two aspects in a cross-sectional in vivo study and in an experimental in vitro study. In the cross-sectional study, 103 men with body mass index (BMI) ≥ 30.0 kg/m 2 were studied; 63 had 24-hr ambulatory blood pressure (ABP) ≥ 130/80 mmHg (ObeseHT) and 40 had 24-hr ABP < 130/80 mmHg (ObeseNT). As controls, we studied 27 men with BMI between 20.0 and 24.9 kg/m 2 and 24-hr ABP < 130/80 mmHg (LeanNT). Serum concentrations of adiponectin and body composition using dual-energy X-ray absorptiometry scanning were determined. In vitro, the direct vasomotor response of adiponectin was tested on subcutaneous resistance arteries from human abdominal adipose tissue. The two obese groups had lower adiponectin concentrations compared with LeanNT (p < 0.01) [median (interquartile range)]: ObeseHT 6.5 (5.1-8.3) mg/L; ObeseNT 6.6 (5.2-7.8) mg/L; and LeanNT 9.4 (6.7-12.4) mg/L, with no significant difference in adiponectin concentrations (or body composition) between ObeseHT and ObeseNT (p = 0.67). In vitro, adiponectin did not have any direct vasodilatory effect and adiponectin did not affect angiotensin II-stimulated vasoconstriction. In conclusion, obese hypertensive men have similar serum concentrations of adiponectin as obese normotensive men. In combination with the in vitro data, these findings question a pathogenic role of adiponectin in human hypertension.High body mass index (BMI) caused by excessive growth of adipose tissue is a major risk factor for hypertension [1], but the mechanisms by which excess adipose tissue leads to hypertension are still not fully elucidated [2,3].Over the past decades, it has become increasingly apparent that adipose tissue is not only a passive energy store, but also an active endocrine and paracrine organ that secretes various proinflammatory, vasoactive and metabolic active substances, collectively called adipocytokines or just adipokines [4][5][6][7][8]. Based on both animal and human studies, it has been suggested that these active adipose tissue-derived substances could play a role in overweight-related diseases, such as type 2 diabetes, coronary heart disease (CHD) and hypertension [4][5][6][7][8].Adiponectin, a 244 amino acid protein, which is secreted from adipose tissue, is one of these adipocytokines [4][5][6][8][9][10]. Compared with other adipocytokines, adiponectin is distinct in the sense that lower (hypoadiponectinaemia) rather than higher (hyperadiponectinaemia) circulating concentrations of adiponectin have been associated with increased risk of overweight-related diseases [4][5][6][8][9][10]. Another distinct feature is that adiponectin has been found to be inversely related to anthropometric measures, ...

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“…Excess visceral fat and IR, but not general adiposity, were independently associated with incident prediabetes and DMII in obese adults [108,148]. Moreover, in mesenteric arteries of morbidly obese individuals, endothelial dysfunction was only observed in the presence of IR, which related to augmented mitochondrial superoxide production and increased systemic inflammation mediated by TNF-α [149]. In addition to its association with systemic vascular inflammation and endothelial dysfunction, IR results in compensatory hyperinsulinemia, which induces LV hypertrophy through activation of the insulin-like growth factor 1 receptors [118].…”

Section: Overweight/obesitymentioning

confidence: 92%