Vascular stiffness in insulin resistance and obesity

Frontiers in Physiology, Год журнала: 2015, Номер 6

Опубликована: Авг. 14, 2015

Obesity, insulin resistance, and type 2 diabetes are associated with a substantially increased prevalence of vascular fibrosis stiffness, attendant risk cardiovascular chronic kidney disease. Although the underlying mechanisms mediators stiffness not well understood, accumulating evidence supports role metabolic immune dysregulation related to adiposity, activation renin angiotensin aldosterone system, reduced bioavailable nitric oxide, extracellular matrix (ECM) ECM remodeling in pathogenesis stiffness. This review will give brief overview relationship between obesity, resistance provide contemporary understanding proposed potential therapeutic strategies.

Язык: Английский

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Uric Acid Promotes Left Ventricular Diastolic Dysfunction in Mice Fed a Western Diet

Hypertension, Год журнала: 2014, Номер 65(3), С. 531 - 539

Опубликована: Дек. 9, 2014

The rising obesity rates parallel increased consumption of a Western diet, high in fat and fructose, which is associated with uric acid. Population-based data support that elevated serum acids are left ventricular hypertrophy diastolic dysfunction. However, the mechanism by excess acid promotes these maladaptive cardiac effects has not been explored. In assessing role diet-induced increases acid, we hypothesized reductions would prevent development cardiomyocyte hypertrophy, stiffness, impaired relaxation reducing growth profibrotic signaling pathways. Four-weeks-old C57BL6/J male mice were fed (46%) fructose (17.5%) or without allopurinol (125 mg/L), xanthine oxidase inhibitor, for 16 weeks. along tissue activity temporally related to body weight, mass, insulin resistance changes blood pressure. diet induced cardiomyocte myocardial oxidative stress, interstitial fibrosis, relaxation. Further, enhanced activation S6 kinase-1 pathway transforming factor-β1/Smad2/3 macrophage proinflammatory polarization. All results improved treatment, lowered as well levels. These findings notion production intake inflammation, stress lead fibrosis

Язык: Английский

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Endothelial Mineralocorticoid Receptor Deletion Prevents Diet-Induced Cardiac Diastolic Dysfunction in Females

Hypertension, Год журнала: 2015, Номер 66(6), С. 1159 - 1167

Опубликована: Окт. 6, 2015

Overnutrition and insulin resistance are especially prominent risk factors for the development of cardiac diastolic dysfunction in females. We recently reported that consumption a Western diet (WD) containing excess fat (46%), sucrose (17.5%), high fructose corn syrup (17.5%) 16 weeks resulted aortic stiffening young female mice these abnormalities were prevented by mineralocorticoid receptor blockade. Herein, we extend those studies testing whether WD-induced contributing to impairment, such as fibrosis, hypertrophy, inflammation, impaired signaling, modulated endothelial cell signaling. Four-week-old knockout wild-type fed mouse chow or WD 4 months. feeding prolonged relaxation time, septal wall motion, increased left ventricular filling pressure indicative dysfunction. This occurred concert with myocardial interstitial fibrosis cardiomyocyte hypertrophy associated enhanced profibrotic (transforming growth factor β1/Smad) progrowth (S6 kinase-1) well oxidative stress proinflammatory immune response. also induced stiffening, assessed ex vivo using atomic force microscopy. Conversely, deficiency dysfunction, profibrotic, conjunction reductions macrophage polarization improvements metabolic Therefore, our findings indicate signaling plays key role activation inflammatory, pathways lead mice.

Язык: Английский

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Capítulo 1 - Conceituação, Epidemiologia e Prevenção Primária

Arquivos Brasileiros de Cardiologia, Год журнала: 2016, Номер 107(3)

Опубликована: Янв. 1, 2016

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Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching

Scientific Reports, Год журнала: 2017, Номер 7(1)

Опубликована: Июль 5, 2017

Obesity increases susceptibility to multiple organ disorders, however, underlying mechanisms remain unclear. The subclinical inflammation assisted by obesity-induced gut permeability may underlie obesity-associated co-morbidities. Despite eminent clinical significance of the obesity led barrier abnormalities, its precise molecular regulation remains It is also unknown whether deregulations, similar gut, characterize other vital organs in obese individuals. claudin family proteins integral tight junction (TJ), apical cell-cell adhesion and a key regulator epithelial barrier. Using comprehensive physiological biochemical analysis intestinal renal tissues from high-fat diet fed mice, critical for maintaining metabolic homeostasis, this study demonstrates that profound TJ-restructuring tissue-specific switching organs. Protein expression cellular distribution were examined. In-silico further highlighted potential association select claudins, modulated obesity, with signaling pathways pathological significance. In vitro studies using Leptin or DCA-treatment suggested causal changes tissue microenvironment regulating deregulations manner. Overall, current findings advances our understanding undertakings associated help predispose specific diseases identifies novel windows preventive and/or therapeutic interventions.

Язык: Английский

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