New developments in the pathogenesis of obesity-induced hypertension.

Introduction: Obesity is a nutritional disorder and associated with excess fat deposition due to altered balance between energy intake and consumption. Obesity and obesity related hypertension are identified as risk factors in development of diabetes and chronic kidney disease. Obesity alters the hemodynamic functions of organs and is a threat for development of cardiovascular diseases, renal failure and peripheral arterial disease. Objectives: The objective of the present study was to compare the renal profile among healthy individuals, obese individuals, obese with preexisting hypertension and obese individuals without hypertension. Materials and Methods: A prospective cross sectional observational study was conducted at ACSR government medical college and hospital, a tertiary care hospital for a period of two years from October 2014 to September 2016. 120 subjects were divided into 4 groups with 30 in each group, healthy, obese, non obese hypertensive and obese hypertensives. Results: All the measured variables in all the four groups of the study were expressed as mean ± standard deviation. BMI of 32.1 ± 2.1 was observed in obese group whereas 22.1 ± 3.1 was observed in healthy group. Statistically significant correlation was found with BMI, S. urea, S. creatinine, S. uricacid and estimated Glomerular filtration rate (‘p’ value

Insulin resistance is frequently associated with obesity-related hypertension. Leptin resistance and increased plasma leptin levels are frequent companions in this association. To examine whether in obesity hypertension with insulin resistance, plus hyperleptinemia, the sodium content of erythrocyte (Naie) reflects a positive sodium balance related to the physiological loss of leptin in sodium reabsorption, we studied a group of obese hypertensive patients, and a group of lean normotensive subjects. In obese hypertensives, fasting glucose, insulin and the insulin resistance index were higher as compared to the lean individuals (107.0 ± 4.1 mg/dl, 10.2 ± 1.4 pU/ml and 2.94 ± 0.52, respectively, vs 98.7 ± 4.1 mg/dl, 7.22 ± 1.33 U/ml, and 1.79 ± 0.16, respectively, p < 0.002). Both the leptin/BMI 2 index as well as the Naie were significantly higher in the obese hypertensive group as compared to control group (1.9± 0.21 vs 1.25 ± 0.27, respectively p < 0.01, and 12.5 ± 0.51 vs 10.7 ± 0.5 mEq/ml/cell, respectively p < 0.05). In obese hypertensives the leptin/BMI 2 index was significantly associated with DBP (r= = 0.41, p < 0.04), MBP (r= 0.44, p < 0.03), Naie (r = 0.41, p < 0.05) and age (r = 0.43, p = 0.03). We conclude that in obese hypertensive patients Naie is increased reflecting a state of positive sodium balance. In these patients, the elevated circulating leptin concentrations were one of the main regulators of the content of sodium in erythrocytes.

Circulating levels of leptin are increased in obesity and have been proposed to contribute to the development of hypertension in obese individuals. Four cardiac hormones, specifically, vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide and atrial natriuretic peptide (ANP), have blood pressure-lowering properties and correlate with the presence of hypertension in obesity. The objective of this study was to determine whether one or more of these cardiac hormones was able to decrease the levels of leptin in the hypothalamus, an area of the brain that has been demonstrated to synthesize more than 40% of leptin in the circulation. The effects of these four cardiac hormones on leptin were examined using dose-response curves in the rat hypothalamus, which synthesizes leptin. Vessel dilator, LANP, kaliuretic peptide and ANP maximally decreased the levels of leptin in hypothalamic cells by 79, 76, 80 and 62%, respectively (P<0.0001 for each). The cardiac hormones decreased leptin levels over a concentration range of 100 pM to 10 μM, with the most significant reductions in leptin levels occurring when the concentrations of the hormones were at micromolar levels. The results of the study suggest that the four cardiac hormones lead to significant reductions in hypothalamic leptin levels, which may be an important mechanism for alleviating leptin-induced hypertension in obesity.

Background.Hypertension is frequently found in obesity, although the mechanisms for obesity related hypertension are still unclear. Several studies showed the role of endothelin-1 in the development of hypertension asso-ciated with obesity. More recent studies showed the possibility for the role of leptin in obesity related hypertension. In vitro study with human umbilical vein endothelial cells (HUVECs) showed correlation between leptin and endothelin-1. The aim of this study was to clarify the relation-ship between leptin, body mass index (BMI), blood pressure (BP) and plasma endothelin-1 in obese hypertensive subjects. Methods.A cross sectional study was performed at National Cardiovas-cular Centre, Harapan Kita Jakarta, which included 80 Indonesian men. The subjects were divided into lean hypertensive and obese hypertensive. The plasma immunoreactive ET-1 and leptin were determined by ELISA method. Results.ET-1 level and leptin level were significantly higher in obese hy-pertensive subjects compared with lean hypertensive subjects. There are significant correlation between endothelin level with BMI (r = 0.32; p < 0.005). There are also significant correlation between leptin level with BMI (r = 0.533; p <0.01), but there are no correlation between plasma leptin and endothelin-1 level in obese hypertensive men. Conclusions.Leptin and ET-1 level were significantly increase in obese hypertensive subjects compared with lean hypertensive subjects. There is no correlation between leptin and ET-1 level in obese hypertensive subjects.

BackgroundRecent observational studies and clinical trials demonstrated an association between gut microbiota and musculoskeletal (MSK) diseases. Nonetheless, whether the gut microbiota composition has a causal effect on the risk of MSK diseases remains unclear.MethodsBased on large-scale genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between gut microbiota and six MSK diseases, namely osteoporosis (OP), fracture, sarcopenia, low back pain (LBP), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Instrumental variables for 211 gut microbiota taxa were obtained from the largest available GWAS meta-analysis (n = 18,340) conducted by the MiBioGen consortium. And the summary-level data for six MSK diseases were derived from published GWAS. The inverse-variance weighted (IVW) method was conducted as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses using multiple methods. The Bonferroni-corrected test was used to determine the strength of the causal relationship between gut microbiota and various MSK diseases. Finally, a reverse MR analysis was applied to evaluate reverse causality.ResultsAccording to the IVW method, we found 57 suggestive causal relationships and 3 significant causal relationships between gut microbiota and MSK diseases. Among them, Genus Bifidobacterium (β: 0.035, 95% CI: 0.013–0.058, p = 0.0002) was associated with increased left handgrip strength, Genus Oxalobacter (OR: 1.151, 95% CI: 1.065–1.245, p = 0.0003) was correlated with an increased risk of LBP, and Family Oxalobacteraceae (OR: 0.792, 95% CI: 0.698–0.899, p = 0.0003) was linked with a decreased risk of RA. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy, or outliers for the causal effect of specific gut microbiota on MSK diseases (p > 0.05). Reverse MR analysis showed fracture may result in a higher abundance of Family Bacteroidales (p = 0.030) and sarcopenia may lead to a higher abundance of Genus Sellimonas (p = 0.032).ConclusionGenetic evidence suggested a causal relationship between specific bacteria taxa and six MSK diseases, which highlights the association of the “gut-bone/muscle” axis. Further exploration of the potential microbiota-related mechanisms of bone and muscle metabolism might provide novel insights into the prevention and treatment of MSK diseases.

The relevance of both hypertension and obesity, as important public health challenges, is increasing worldwide. Compared with the year 2000, the number of adults with hypertension is predicted to increase by 60% to a total of 1.56 billion by the year 2025 [1]. The growing prevalence of obesity is increasingly recognized as one of the most important risk factors for the development of hypertension. This epidemic of obesity and obesity-related hypertension is paralleled by an alarming increase in the incidence of diabetes mellitus and chronic kidney disease. This editorial examines the evidence linking obesity with hypertension, reviews the mechanisms underlying this link, and discusses its potential implications for renal disease. Earlier studies attributed the link between obesity and hypertension primarily to haemodynamic factors. Recent evidence indicates that the association is much more complex than initially thought.

The present study was aimed to reveal the relationship between uric acid and fructose-induced obesity hypertension and its mechanisms. A rat model with obesity hypertension was induced by a high-fructose diet. In the experiment I, the rats were fed with fructose for 8 wks along with allopurinol or benzbromarone at the beginning. In the experiment II, the rats were fed with fructose for 8 wks firstly. And then, these rats were treated with allopurinol or benzbromarone for additional 6 wks. Fructose-fed rats showed hyperuricemia, abdominal obesity hypertension and an activation in adipose renin-angiotensin system (RAS). Also, fructose-fed rats had higher levels of proinflammatory cytokines and more macrophages infiltrating in adipose tissue. In the experiment I, allopurinol and benzbromarone significantly reduced serum uric acid at 8 wk. Adipose RAS overactivation, adipose inflammatory responses and the development of obesity hypertension were all effectively prevented by hyperuricemia inhibition. In the experiment II, 6-wk treatment with allopurinol and benzbromarone significantly decreased serum uric acid, downregulated adipose RAS, abolished adipose inflammation and improved obesity hypertension. In conclusion, urate-lowering therapy protects rats against fructose-induced obesity hypertension. The mechanisms appear to be via downregulated adipose RAS and reduced inflammation in adipose tissue.

Obesity, impaired glucose tolerance, and diabetes mellitus are associated with a substantially increased prevalence of hypertension, cardiovascular (CVD), and chronic renal disease. The prevalence of hypertension in patients who have type 2 diabetes mellitus is up to 3 times higher than in patients without diabetes mellitus. Further, the coexistence of hypertension in diabetic patients greatly enhances their likelihood of developing CVD and chronic kidney disease.1–4 Indeed, studies conducted in the Framingham population with diabetes mellitus1 indicated that the presence of hypertension in these participants was a resulting risk factor for the presence of CVD. This data and other studies suggest a 2-fold increased risk of CVD events and deaths in diabetic persons with hypertension compared with those with normal blood pressures. The increased association between hypertension and diabetes mellitus can be explained, in part, by the presence of a maladaptive interaction of factors, such as excessive caloric intake/decreased activity and associated insulin resistance (IR), chronic activation of the renin–angiotensin (Ang II)–aldosterone system (RAAS), the sympathetic nervous system, and abnormalities of innate immunity, inflammation, and oxidative stress1–21 (Figure). The epidemic of obesity and sedentary lifestyle, and the aging of populations worldwide have contributed to the current high prevalence of diabetes mellitus and hypertension. Figure. Systemic and metabolic factors that promote coexistent diabetes mellitus, hypertension, cardiovascular, and chronic kidney disease. Hypertension is more common in diabetic patients than in the general population.1–4 In the Strong Heart Study, baseline measurements which independently predicted incident hypertension, included waist circumference, elevations in baseline systolic blood pressure, and left ventricular mass and diabetes mellitus.2 Further, a recent longitudinal Japanese study of 5198 subjects showed that parental hypertension has an age-independent impact on both male and female offspring in elevations in blood pressure, plasma glucose, and triglyceride …

Unmasking Hormonal Mechanisms of Hypertension in Obesity.

Autonomic nervous system (ANS) activity in overweight individuals has been characterized by low parasympathetic (PNS) and elevated sympathetic (SNS) activity. Continuously elevated SNS activity has been associated with an increased risk of cardiac complications. Thus, individuals at high risk for experiencing a cardiac event should be cautious of exaggerated elevations in SNS activity during and after physical exertion. PURPOSE: To assess ANS modulation via heart rate variability (HRV) in overweight and normal weight individuals prior to, during, and following moderate exercise. METHODS: Four overweight and obese (OW; 4 males; age: 27.5±3.1 years; BMI: 31.3±5.4 kg/m2) and four normal weight (NW; 2 males and 2 females; age: 27.5±3.4 years; BMI 23.2±1.4 kg/m2) adults participated in this study. During the initial visit, height, weight, and maximal oxygen consumption (VO2max) were evaluated. On a separate day, participants were asked to be seated at rest for 10 min and then cycled for 15-min at 75% of their VO2max. HRV indices [low and high frequency bands, their ratio, the square root of the mean of squared differences between successive RR intervals (RMSSD), and the percentage of successive normal-to-normal intervals greater than 50 ms (pNN50)] and respiratory rate were measured for 10-min at baseline, 10-min during exercise, and 10-min post-exercise. RESULTS: BMI was significantly different between groups (P<0.05). Heart rate was significantly higher during exercise in OW (148.1±10.6 bpm) compared to NW (130.1±6.8 bpm) (P<0.05). RMSSD was significantly different between groups during exercise (OW: 2.5±0.5 ms; NW: 5.0±1.9 ms) and at post-exercise (OW: 8.7±3.9 ms; NW: 21.5±7.8 ms). PNN50 was significantly lower in OW (0.2±0.3%) compared to NW (2.5±1.7%) at post-exercise. Respiratory rate was similar between groups at all time points. CONLUSION: These data suggest that ANS modulation in overweight and obese individuals during and immediately following exercise is characterized by low PNS and high SNS activity, compared to normal weight individuals exercising at the same relative intensity. Future research should further investigate the relationship between post-exercise ANS activity and the risk of cardiac complications, particularly among exercising overweight and obese individuals.

Emerging evidence suggests that gut microbiota imbalances may influence the onset of musculoskeletal disorders (MSDs), yet conclusive evidence establishing causation remains limited. This study investigates the causal relationship between gut microbiota and a range of MSDs, aiming to identify potential therapeutic targets. Using data on 211 gut microbiome taxa from a genome-wide association study (GWAS) and summary statistics for 26 MSDs from the Finnish Biobank, we employed Mendelian randomization (MR) with inverse-variance weighting (IVW) as the primary analytical approach, complemented by Bayesian model validation to ensure robust results. Our MR analyses revealed significant causal associations between gut microbiota and nine MSDs within four categories, including osteoporosis (IVW-Beta = 0.011, P = 0.025), rheumatoid arthritis (IVW-Beta = − 0.016, P < 0.001), rotator cuff syndrome (IVW-Beta = − 0.007, P = 0.022), and calcific tendonitis of the shoulder (IVW-Beta = − 0.021, P = 0.034). Bayesian validation underscored the plausibility of these relationships, supporting the potential causal role of gut microbiota in the development of these disorders. Our findings present a library of causal associations that underscore the gut microbiome's role in MSD pathogenesis, providing genetic evidence that highlights specific gut microbiota taxa as prospective therapeutic targets. This research offers novel insights into the pathogenic mechanisms underlying MSDs and points toward new directions for future investigation into microbiome-based therapies.

Nocturnal reduction of blood pressure and the antihypertensive response to a diuretic or angiotensin converting enzyme inhibitor in obese hypertensive patients

Purpose of reviewThe prevalence of both obesity and hypertension is increasing in childhood, with considerable overlap in disease and causative factors. Evidence from studies over the past decade suggests both obesity and hypertension have summative effects on both cardiac remodelling in childhood and major adverse cardiovascular events in adulthood.Recent findingsWe highlight recent high-quality evidence reporting epidemiology of obesity, hypertension and hypertension-mediated organ damage (HMOD) in those with obesity-related hypertension. We discuss the early life influences on BP and BMI trajectory and the clustering of cardiovascular risk factors (CVRFs) seen in obesity hypertension. We discuss management options highlighting key contributors to compounding risk for obesity-associated hypertension across the first two decades of life, with potential windows for both individual and population-level intervention.SummaryCurrently, a large and expanding cohort of young people with multiple CVRFs is progressing toward adulthood, where they are likely to experience disproportionate cardiovascular morbidity when compared with age-matched healthy peers. These trends underscore the urgent need for co-ordinated healthcare responses to manage affected children and for robust governmental and public-health interventions to mitigate the environmental and societal drivers of this convergent epidemic.

An overview of microbiome based strategies on anti‐obesity

Hypertension is a chronic cardiovascular disease that significantly impacts human quality of life. Gut microbiota and its metabolites have been reported to be involved in lipid metabolism and blood pressure regulation, but the specific alterations and pathogenic mechanisms of gut microbiota in obesity-related hypertension (OrHTN) remain unclear. In this study, we observed a significant proliferation of Desulfobacterota and Proteobacteria, while a decrease in the abundance of several butyrate-producing bacterial genera, accompanied by decreased fecal and plasma butyrate levels in high-fat diet (HFD)-induced OrHTN rats. Histone 3 lysine 9 butyrylation (H3K9bu) modification in the kidney of OrHTN rats was reduced and downregulated the expression of the hypertension-related gene MAS1. Subsequent transplantation of cecal contents from OrHTN rats on HFD into recipient rats on a normal chow diet resulted in hypertension but without obesity. Furthermore, in vitro experiments suggested that sodium butyrate increased H3K9bu modification and the expression of MAS1 in a concentration-dependent manner. In conclusion, our findings suggest that gut microbiota may contribute to the development of OrHTN by altering the expression of hypertension-related genes through butyrate-mediated histone butyrylation. This work may provide new insights into the prevention and treatment of hypertension by targeting the regulation of gut microbiota and metabolites.