scholarly journals Na+-sensitive elevation in blood pressure is ENaC independent in diet-induced obesity and insulin resistance

2016 ◽  
Vol 310 (9) ◽  
pp. F812-F820 ◽  
Author(s):  
Jonathan M. Nizar ◽  
Wuxing Dong ◽  
Robert B. McClellan ◽  
Mariana Labarca ◽  
Yuehan Zhou ◽  
...  

The majority of patients with obesity, insulin resistance, and metabolic syndrome have hypertension, but the mechanisms of hypertension are poorly understood. In these patients, impaired sodium excretion is critical for the genesis of Na+-sensitive hypertension, and prior studies have proposed a role for the epithelial Na+ channel (ENaC) in this syndrome. We characterized high fat-fed mice as a model in which to study the contribution of ENaC-mediated Na+ reabsorption in obesity and insulin resistance. High fat-fed mice demonstrated impaired Na+ excretion and elevated blood pressure, which was significantly higher on a high-Na+ diet compared with low fat-fed control mice. However, high fat-fed mice had no increase in ENaC activity as measured by Na+ transport across microperfused cortical collecting ducts, electrolyte excretion, or blood pressure. In addition, we found no difference in endogenous urinary aldosterone excretion between groups on a normal or high-Na+ diet. High fat-fed mice provide a model of metabolic syndrome, recapitulating obesity, insulin resistance, impaired natriuresis, and a Na+-sensitive elevation in blood pressure. Surprisingly, in contrast to previous studies, our data demonstrate that high fat feeding of mice impairs natriuresis and produces elevated blood pressure that is independent of ENaC activity and likely caused by increased Na+ reabsorption upstream of the aldosterone-sensitive distal nephron.

2019 ◽  
Vol 26 (2_suppl) ◽  
pp. 33-46 ◽  
Author(s):  
Peter M Nilsson ◽  
Jaakko Tuomilehto ◽  
Lars Rydén

A cluster of metabolic factors have been merged into an entity named the metabolic syndrome. Although the characteristics of this syndrome have varied over time the presently used definition was established in 2009. The presence of three abnormal findings out of five components qualifies a person for the metabolic syndrome: elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure and elevated fasting plasma glucose. Cut points have been defined for all components apart from waist circumference, for which national or regional values are used. The metabolic syndrome predicts cardiovascular disease and type 2 diabetes. This associated risk does not exceed its components whereof elevated blood pressure is the most frequent. A successful management should, however, address all factors involved. The management is always based on healthy lifestyle choices but has not infrequently to be supported by pharmacological treatment, especially blood pressure lowering drugs. The metabolic syndrome is a useful example of the importance of multiple targets for preventive interventions. To be successful management has to be individualized not the least when it comes to pharmacological therapy. Frail elderly people should not be over-treated. Knowledge transfer of how risk factors act should be accompanied by continuous trust building and motivation. In complex situations with a mix of biological risk factors, adverse social conditions and unhealthy lifestyle, everything cannot be changed at once. It is better to aim for small steps that are lasting than large, unsustainable steps with relapses to unhealthy behaviours. A person with the metabolic syndrome will always be afflicted by its components, which is the reason that management has to be sustained over a very long time. This review summarizes the knowledge on the metabolic syndrome and its management according to present state of the art.


2019 ◽  
Vol 8 (6) ◽  
pp. 817 ◽  
Author(s):  
Yi-Cheng Chang ◽  
Shih-Che Hua ◽  
Chia-Hsuin Chang ◽  
Wei-Yi Kao ◽  
Hsiao-Lin Lee ◽  
...  

(1) Background: Overt and subclinical hypothyroidism has been associated with increased cardiometabolic risks. Here we further explore whether thyroid function within normal range is associated with cardiometabolic risk factors in a large population-based study. (2) Methods: We screened 24,765 adults participating in health examinations in Taiwan. Participants were grouped according to high-sensitive thyroid-stimulating hormone (hsTSH) level as: <50th percentile (0.47–1.48 mIU/L, the reference group), 50–60th percentile (1.49–1.68 mIU/L), 60–70th percentile (1.69–1.94 mIU/L), 70–80th percentile (1.95–2.3 mIU/L), 80–90th percentile (2.31–2.93 mIU/L), and >90th percentile (>2.93 mIU/L). Cardiometabolic traits of each percentile were compared with the reference group. (3) Results: Elevated hsTSH levels within normal range were dose-dependently associated with increased body mass index, body fat percentage, waist circumferences, blood pressure, hemoglobin A1c (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high homeostasis model of assessment of beta-cell (HOMA-β), triglycerides, total cholesterols, fibrinogen, and uric acids (p-for-trend <0.001), but not with fasting glucose levels. The association remained significant after adjustment of age, sex, and lifestyle. As compared to the reference group, subjects with the highest hsTSH percentile had significantly increased risk of being overweight (adjusted odds ratio (adjOR): 1.35), increased body fat (adjOR: 1.29), central obesity (adjOR: 1.36), elevated blood pressure (adjOR: 1.26), high HbA1c (adjOR: 1.20), hyperinsulinemia (adjOR: 1.75), increased HOMA-IR (adjOR: 1.45), increased HOMA-β (adjOR: 1.40), hypertriglyceridemia (adjOR: 1.60), hypercholesterolemia (adjOR: 1.25), elevated hsCRP (adjOR: 1.34), increased fibrinogen (adjOR: 1.45), hyperuricemia (adjOR: 1.47), and metabolic syndrome (adjOR: 1.42), but significant risk of low fasting glucose (adjOR: 0.89). Mediation analysis indicates that insulin resistance mediates the majority of the association between thyroid hormone status and the metabolic syndrome. (4) Conclusion: Elevated hsTSH within the normal range is a cardiometabolic risk marker associated with central obesity, insulin resistance, elevated blood pressure, dyslipidemia, hyperuricemia, inflammation, and hypercoagulability.


Vascular ◽  
2012 ◽  
Vol 20 (3) ◽  
pp. 156-165 ◽  
Author(s):  
Daynene Vykoukal ◽  
Mark G Davies

Metabolic syndrome is highly prevalent in vascular patients and has a significant impact on the outcomes of vascular interventions. It comprises of a set of metabolically driven risk factors, including truncal obesity, dyslipidemia, elevated blood pressure and elevated fasting blood glucose. Increased insulin resistance within the context of obesity and hypertension contributes to atherogenic dyslipidemia, hyperglycemia, and prothrombotic and proinflammatory states which lead to the adverse impact of metabolic syndrome on the response to injury and on atherosclerotic disease progression. This review focuses on the complex biology of metabolic syndrome and its relevance to management of vascular patients, including outcomes and implications for the coronary, cerebrovascular and lower-extremity vascular beds.


2017 ◽  
Vol 6 (4) ◽  
pp. 278-288 ◽  
Author(s):  
Sandra N Slagter ◽  
Robert P van Waateringe ◽  
André P van Beek ◽  
Melanie M van der Klauw ◽  
Bruce H R Wolffenbuttel ◽  
...  

Introduction To evaluate the prevalence of metabolic syndrome (MetS) and its individual components within sex-, body mass index (BMI)- and age combined clusters. In addition, we used the age-adjusted blood pressure thresholds to demonstrate the effect on the prevalence of MetS and elevated blood pressure. Subjects and methods Cross-sectional data from 74,531 Western European participants, aged 18–79 years, were used from the Dutch Lifelines Cohort Study. MetS was defined according to the revised NCEP-ATPIII. Age-adjusted blood pressure thresholds were defined as recommended by the eight reports of the Joint National Committee (≥140/90 mmHg for those aged <60 years, and ≥150/90 mmHg for those aged ≥60 years). Results 19.2% men and 12.1% women had MetS. MetS prevalence increased with BMI and age. Independent of BMI, abdominal obesity dominated MetS prevalence especially in women, while elevated blood pressure was already highly prevalent among young men. Applying age-adjusted blood pressure thresholds resulted in a 0.2–11.9% prevalence drop in MetS and 6.0–36.3% prevalence drop in elevated blood pressure, within the combined sex, BMI and age clusters. Conclusions We observed a gender disparity with age and BMI for the prevalence of MetS and, especially, abdominal obesity and elevated blood pressure. The strict threshold level for elevated blood pressure in the revised NCEP-ATPIII, results in an overestimation of MetS prevalence.


PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0218307 ◽  
Author(s):  
Winnie W. Yu ◽  
Arshdeep K. Randhawa ◽  
Steven N. Blair ◽  
Xuemei Sui ◽  
Jennifer L. Kuk

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Zheng ◽  
Zengshuo Xie ◽  
Jiayong Li ◽  
Chen Chen ◽  
Wenting Cai ◽  
...  

Abstract Background Recent studies have reported the effects of metabolic syndrome (MetS) and its components on atrial fibrillation (AF), but the results remain controversial. Therefore, we performed a meta-analysis to evaluate the relationship between MetS and AF risk. Methods Studies were searched from the Cochrane library, PubMed, and Embase databases through May 2020. Adjusted hazard ratios (HRs) and its corresponding 95% confidence intervals (CIs) were extracted and then pooled by using a random effects model. Results A total of 6 observational cohort studies were finally included. In the pooled analysis, MetS was associated with an increased risk of AF (HR 1.57; 95% CI 1.40–1.77; P < 0.01). And the components of MetS including abdominal obesity (HR 1.37; 95% CI 1.36–1.38; P < 0.01), elevated blood pressure (HR 1.56; 95% CI 1.46–1.66; P < 0.01), elevated fasting glucose (HR 1.18; 95% CI 1.15–1.21; P < 0.01) and low high density cholesterol (HDL) (HR 1.18; 95% CI 1.06–1.32; P < 0.01) was also associated with an increased risk of AF, while high triglyceride (HR 0.99; 95% CI 0.87–1.11, P = 0.82) was not. Conclusions Our present meta-analysis suggested that MetS, as well as its components including abdominal obesity, elevated blood pressure, elevated fasting glucose and low HDL cholesterol were associated with an increase in the risk of AF.


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