Endothelial Mineralocorticoid Receptor Deletion Prevents Diet-Induced Cardiac Diastolic Dysfunction in Females DOI Open Access
Guanghong Jia,

Javad Habibi,

Vincent G. DeMarco

et al.

Hypertension, Journal Year: 2015, Volume and Issue: 66(6), P. 1159 - 1167

Published: Oct. 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.

Language: Английский

Obesity-Induced Hypertension DOI
John E. Hall, Jussara M. do Carmo, Alexandre A. da Silva

et al.

Circulation Research, Journal Year: 2015, Volume and Issue: 116(6), P. 991 - 1006

Published: March 12, 2015

Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 75% the risk human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity The mediators abnormal kidney function blood during development hypertension include (1) physical compression kidneys by fat around kidneys, (2) activation renin–angiotensin–aldosterone system, (3) sympathetic nervous system activity. Activation likely due, part, compression, as well activation. However, also causes mineralocorticoid receptor independent aldosterone or angiotensin II. mechanisms have not been fully elucidated but may require leptin brain melanocortin system. With prolonged target organ injury, obesity-associated becomes more difficult control, often requiring multiple antihypertensive drugs treatment other factors, including dyslipidemia, insulin resistance diabetes mellitus, inflammation. Unless effective antiobesity are developed, effect on related cardiovascular, metabolic disorders become even future prevalence continues increase.

Language: Английский

Citations

1028
Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy DOI
Guanghong Jia, Vincent G. DeMarco, James R. Sowers

et al.

Nature Reviews Endocrinology, Journal Year: 2015, Volume and Issue: 12(3), P. 144 - 153

Published: Dec. 18, 2015

Language: Английский

Citations

789
Obesity, kidney dysfunction and hypertension: mechanistic links DOI
John E. Hall, Jussara M. do Carmo, Alexandre A. da Silva

et al.

Nature Reviews Nephrology, Journal Year: 2019, Volume and Issue: 15(6), P. 367 - 385

Published: April 23, 2019

Language: Английский

Citations

494
Prevention and Control of Hypertension DOI
Robert M. Carey, Paul Muntner, Hayden B. Bosworth

et al.

Journal of the American College of Cardiology, Journal Year: 2018, Volume and Issue: 72(11), P. 1278 - 1293

Published: Sept. 1, 2018

Language: Английский

Citations

422
Effects of Exercise to Improve Cardiovascular Health DOI Creative Commons

Kelsey M. Pinckard,

Kedryn K. Baskin, Kristin I. Stanford

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2019, Volume and Issue: 6

Published: June 4, 2019

Obesity is a complex disease that affects whole body metabolism and associated with an increased risk of cardiovascular (CVD) Type 2 diabetes (T2D). Physical exercise results in numerous health benefits important tool to combat obesity its co-morbidities, including disease. Exercise prevents both the onset development therapeutic improve outcomes for patients Some include enhanced mitochondrial function, restoration improvement vasculature, release myokines from skeletal muscle preserve or augment function. In this review we will discuss mechanisms through which promotes health.

Language: Английский

Citations

321
Discrepant gut microbiota markers for the classification of obesity-related metabolic abnormalities DOI Creative Commons
Qiang Zeng, Dongfang Li, Yuan He

et al.

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: Sept. 17, 2019

Abstract The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for in patients with different abnormalities investigate their relationships clinical indicators, 1,914 Chinese adults were enrolled 16S rRNA gene sequencing this retrospective study. Based on composition, Random forest classifiers constructed screen the (Group OA) or without diseases O) from healthy individuals H), high accuracies observed discrimination of Group O OA (areas under receiver operating curve (AUC) equal 0.68 0.76, respectively). Furthermore, six shared by various disorders ( Bacteroides , Parabacteroides Blautia Alistipes Romboutsia Roseburia ). As O, exhibited low accuracy (AUC = 0.57). Nonetheless, classifications distinguish between obese specific not accurate values 0.59 0.66). Common biomarkers identified uric acid, serum lipids blood pressure, such as Clostridium XIVa, . A total 20 genera associated multiple significant indicators. For example, Ruminococcus2 sensu stricto Dorea positively correlated indicators bodyweight (including waistline body mass index) density lipoprotein, triglyceride cholesterol). In contrast, aforementioned negatively Butyricicoccus Alistipes, Parasutterella IV Generally, these hold potential predict obesity-related abnormalities, interventions based might be beneficial weight loss risk improvement.

Language: Английский

Citations

315
Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis DOI Open Access
Jianye Dai, Kai Liang, Shan Zhao

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(26)

Published: June 11, 2018

Significance Baicalin is a major flavonoid component from the herbal medicine Scutellaria baicalensis that has been shown to have an antisteatosis effect. Through quantitative chemoproteomic profiling, we discovered baicalin acts as natural allosteric activator of carnitine palmitoyltransferase 1 (CPT1), rate-limiting enzyme fatty acid β-oxidation (FAO). By directly binding CPT1 and activating its activity accelerate degradation, can significantly ameliorate symptoms associated with hepatic steatosis reduce diet-induced obesity (DIO). Our study provides example product agonist for CPT1. The results provide mechanistic insights explain bioactivity in reducing lipid accumulation introduce exciting opportunities developing novel flavonoid-based FAO activators pharmacologically treating DIO metabolic disorders.

Language: Английский

Citations

273
Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited DOI Creative Commons
Alexandre A. da Silva, Jussara M. do Carmo, Xuan Li

et al.

Canadian Journal of Cardiology, Journal Year: 2020, Volume and Issue: 36(5), P. 671 - 682

Published: Feb. 12, 2020

Citations

263
Obesity, Adipose Tissue and Vascular Dysfunction DOI Open Access
Mascha Koenen, Michael A. Hill, Paul Cohen

et al.

Circulation Research, Journal Year: 2021, Volume and Issue: 128(7), P. 951 - 968

Published: April 1, 2021

Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity strongly associated with comorbidities such as hypertension insulin resistance, which collectively contribute to development cardiovascular resultant morbidity mortality. Forty-two percent adults in United States obese, a total 1.9 billion worldwide overweight or obese. These alarming numbers, continue climb, represent major health economic burden. Adipose tissue is highly dynamic organ that can be classified based on cellular composition different depots their distinct anatomical localization. Massive expansion remodeling adipose during differentially affects specific significantly contributes vascular dysfunction diseases. Visceral accumulation results increased immune cell infiltration secretion vasoconstrictor mediators, whereas subcutaneous less harmful. Therefore, fat distribution more than overall body weight key determinant risk for Thermogenic brown beige tissue, contrast white beneficial effects vasculature. The relationship between type its influence function becomes particularly evident context heterogenous phenotype perivascular location dependent. In this review, we address abnormal how critically hypertension, endothelial dysfunction, stiffness. We also discuss local systemic roles derived secreted factors inflammation highlight detrimental impact health.

Language: Английский

Citations

261
Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications DOI
Jun Ren, Ne N. Wu, Shuyi Wang

et al.

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(4), P. 1745 - 1807

Published: May 5, 2021

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to rapidly increased overweight obesity. To this point, epidemiological, clinical, experimental evidence supports existence unique disease entity termed "obesity cardiomyopathy," which develops independent hypertension, coronary disease, other diseases. Our contemporary review evaluates for pathological condition, examines putative responsible mechanisms, discusses therapeutic options disorder. Clinical findings have consolidated presence left ventricular dysfunction Experimental investigations uncovered pathophysiological changes myocardial structure function genetically predisposed diet-induced Indeed, consolidates wide array cellular molecular mechanisms underlying etiology obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover free fatty acids, lipotoxicity, amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, fibrosis, dampened flow reserve, microvascular (microangiopathy), endothelial impairment. Given important role risk failure, that with preserved systolic recent rises COVID-19-associated cardiovascular mortality, should provide compelling cardiomyopathy, various comorbid conditions, offer new insights into potential approaches (pharmacological lifestyle modification) clinical management cardiomyopathy.

Language: Английский

Citations

252