Microbial DNA Enrichment Promotes Adrenomedullary Inflammation, Catecholamine Secretion, and Hypertension in Obese Mice.

Background Obesity is an established risk factor for hypertension. Although obesity-induced gut barrier breach leads to the leakage of various microbiota-derived products into host circulation and distal organs, the roles of microbiota in mediating the development of obesity-associated adrenomedullary disorders and hypertension have not been elucidated. We seek to explore the impacts of microbial DNA enrichment on inducing obesity-related adrenomedullary abnormalities and hypertension. Methods and Results Obesity was accompanied by remarkable bacterial DNA accumulation and elevated inflammation in the adrenal glands. Gut microbial DNA containing extracellular vesicles (mEVs) were readily leaked into the bloodstream and infiltrated into the adrenal glands in obese mice, causing microbial DNA enrichment. In lean wild-type mice, adrenal macrophages expressed CRIg (complement receptor of the immunoglobulin superfamily) that efficiently blocks the infiltration of gut mEVs. In contrast, the adrenal CRIg+ cell population was greatly decreased in obese mice. In lean CRIg-/- or C3-/- (complement component 3) mice intravenously injected with gut mEVs, adrenal microbial DNA accumulation elevated adrenal inflammation and norepinephrine secretion, concomitant with hypertension. In addition, microbial DNA promoted inflammatory responses and norepinephrine production in rat pheochromocytoma PC12 cells treated with gut mEVs. Depletion of microbial DNA cargo markedly blunted the effects of gut mEVs. We also validated that activation of cGAS (cyclic GMP-AMP synthase)/STING (cyclic GMP-AMP receptor stimulator of interferon genes) signaling is required for the ability of microbial DNA to trigger adrenomedullary dysfunctions in both in vivo and in vitro experiments. Restoring CRIg+ cells in obese mice decreased microbial DNA abundance, inflammation, and hypertension. Conclusions The leakage of gut mEVs leads to adrenal enrichment of microbial DNA that are pathogenic to induce obesity-associated adrenomedullary abnormalities and hypertension. Recovering the CRIg+ macrophage population attenuates obesity-induced adrenomedullary disorders.

Temporal patterns of alterations in obesity index, lipid profile, renal function and blood pressure during the development of hypertension in male, but not female, rats fed a moderately high-fat diet.

CONTEXT: Male Sprague-Dawley rats consuming a moderately high-fat (MHF)-diet diverge into obesity-prone (OP) with hypertension and obesity-resistant. OBJECTIVES: To study the temporal inter-relationships between body-weight, obesity-index, plasma lipid-profile, renal functional parameters and systolic-pressure alterations during 10-weeks feeding MHF or normal diet to male and female rats. METHODS: Body-weight, obesity-index and systolic-pressure were measured weekly, while metabolic-cage and blood-sampling protocols were performed every other week. After 10-weeks, renal excretory responses to acute salt-loading and renal autoregulation were examined. RESULTS: The male-OP group had progressively increased body-weight, plasma-triglyceride and systolic-pressure from Weeks 2, 4 and 5, respectively, lower renal sodium-excretion at weeks 4-8 and finally, delayed excretory response to salt-loading and rightward and downward shifts in renal autoregulatory curves compared to all other groups. CONCLUSION: Feeding the MHF-diet in male-OP rats led to a greater weight-gain and adiposity followed by the development of atherogenic-hyperlipidaemia and persistently impaired pressure-natriuresis to induce hypertension.

Bilateral renal denervation prevents the development of hypertension during diet-induced obesity in male rats.

NEW FINDINGS: What is the central question of this study? What is the role of the renal nerves in the development of obesity, hyperlipidaemia and hypertension during the long-term feeding of a moderately high-fat diet in male obesity-prone rats? What is the main finding and its importance? The renal nerves play a prominent mediatory role, without influencing the establishment of visceral adiposity and atherogenic hyperlipidaemia, in the induction and progression of pressure natriuresis impairment and hypertension during the developmental period of diet-induced obesity. ABSTRACT: Feeding a moderately high-fat (MHF) diet in male Sprague-Dawley rats induces obesity, pressure natriuresis impairment and hypertension. This study investigated the role of the renal nerves in the impaired pressure natriuresis and hypertension caused by feeding a MHF diet. After collecting baseline data on day 0, 12 rats remained on a low-fat diet (LF group) while the others were switched onto a MHF diet and diverged into obesity-resistant (OR) or obesity-prone (OP). After 4 weeks, half of the OR and OP rats underwent bilateral renal denervation (BRD) to generate four groups: OR, OR/BRD, OP and OP/BRD (n = 12). During 10 weeks, body weight, obesity index, systolic pressure and renal excretory function were measured regularly. After 10 weeks, renal excretory responses to acute salt loading and renal autoregulation were evaluated. The OP and OP/BRD groups had greater increases of body weight and obesity index during the dietary period compared to the other groups, and by week 10 their body weight (425.1 ± 7.2 and 411.9 ± 5.1 g) became considerably larger than that of the LF group (358.5 ± 6.2 g). Renal sodium excretion was reduced by ∼20% at week 4 in the OP and OP/BRD groups, while only the OP group had lower sodium excretion at weeks 6-8 and higher systolic pressure over weeks 5-10 than the other groups and its week 10 systolic pressure reached 138.1 ± 6.7 versus 123.6 ± 2.7 mmHg of the LF group. The OP group showed delayed renal excretory responses to salt loading with rightward and downward shifts in renal autoregulatory curves. Therefore, the renal nerves exert a main mediatory role in the development of pressure natriuresis impairment and hypertension as obesity is established due to the long-term consumption of the MHF diet in male OP rats.

Obesity in patients with hypertension attending a medical outpatient clinic in a tertiary health facility in Enugu, Southeast Nigeria.

Introduction: The prevalence of obesity is increasing in sub-Saharan Africa which reflects the current global trend. Epidemiological data have consistently shown a strong relationship between obesity and hypertension in Africans, and this association is stronger for central obesity. The aim of this study was to describe the pattern of overweight/obesity among patients living with hypertension in a tertiary hospital in Enugu, Southeast Nigeria. Methods: This was a cross-sectional study conducted in the Medical Out-Patient Clinic of the Enugu State University Teaching Hospital in Enugu, Enugu State, Southeast Nigeria. Data were analyzed using the SPSS version 22. Results: Data were collected from a total of 450 consenting patients, most of whom 64% (288) were females. The mean body mass index (BMI) was 28.9 ± 6.1 kg/m2 higher in females than males (29.8 ± 6.5 kg/m2 vs. 26.7 ± 5.2 kg/m2, P < 0.001). The gender distribution of classes of obesity showed female preponderance. A little more than one-third of the patients were overweight, whereas about four out of every ten patients were obese. While overweight did not differ significantly across gendeWr (P = 0.67), more feWmales than males were significantly obese (P < 0.001). The age distribution of BMI showed increasing rates of underweight and decreasing rate of morbid obesity with age. About 86.8% of the females had substantially increased waist circumference compared to 26.5% of the males. Overall, 53% of the males and 97.6% of the females have abnormal waist circumferences. Waist-hip ratio was equally abnormal in 89.3% of the study population even though no statistically significant difference was observed across gender. Conclusion: Overweight and obesity are common among patients with hypertension as demonstrated in this study. There is need to set up an aspect of health education which specifically sensitizes the public against the untoward consequences of overweight and obesity.

RésuméIntroduction: La prévalence de l'obésité augmente en Afrique subsaharienne (ASS), ce qui reflète la tendance mondiale actuelle. Les données épidémiologiques ont constamment montré une forte relation entre l'obésité et l'hypertension chez les Africains et cette association est plus forte pour l'obésité centrale. Le but de cette étude était de décrire le schéma de surpoids / obésité chez les patients souffrant d'hypertension dans un hôpital tertiaire à Enugu, dans le sud-est du Nigeria. Méthodes: Il s'agit d'une étude transversale menée dans la clinique de consultations externes de l'hôpital universitaire d'Enugu State University à Enugu, dans l'État d'Enugu, dans le sud-est du Nigéria. Les données ont été analysées à l'aide de la version 22 de SPSS. Résultats: Les données ont été recueillies auprès d'un total de 450 patients consentants, dont 64% (288) étaient des femmes. L'IMC moyen était de 28,9 ± 6,1) kg / m2 plus élevé chez les femmes que chez les hommes 29,8 ± 6,5) kg / m2 contre 26,7 ± 5,2 kg / m2, p <0,001). La répartition par sexe des classes d'obésité a montré une prépondérance féminine. Un peu plus d'un tiers des patients étaient en surpoids, tandis qu'environ quatre patients sur dix étaient obèses. Bien que le surpoids ne diffère pas significativement selon le sexe (p = 0,67), plus de femmes que d'hommes étaient significativement obèses. (P <0,001). La répartition par âge de l'IMC a montré une augmentation du taux d'insuffisance pondérale et une diminution du taux d'obésité morbide avec l'âge. Environ 86,8% des femmes avaient considérablement augmenté le tour de taille, contre 26,5% des hommes. Dans l'ensemble, 53% des hommes et 97,6% des femmes ont des circonférences de taille anormales. Le rapport taille / hanche était également anormal et anormal dans 89,3% de la population étudiée, même si aucune différence statistiquement significative n'a été observée entre les sexes. Conclusion: Le surpoids et l'obésité sont courants chez les patients souffrant d'hypertension, comme démontré dans cette étude. Il est nécessaire de mettre en place un aspect de l'éducation sanitaire qui sensibilise spécifiquement le public aux conséquences fâcheuses du surpoids et de l'obésité.

Hydroethanolic Extract of A. officinarum Hance Ameliorates Hypertension and Causes Diuresis in Obesogenic Feed-Fed Rat Model.

Alpinia officinarum Hance (Zingiberaceae) has been used widely in traditional Chinese and Ayurvedic medicines. Its folkloric uses include relieving stomach ache, treating cold, improving the circulatory system, and reducing swelling. Its effectiveness and mechanism of antihypertension in obesity-induced hypertensive rats have not been studied yet as per our knowledge. This study has been designed to provide evidence of underlying mechanisms to the medicinal use of A. officinarum as a cardiotonic using an obesity-induced hypertension model in rats. Chronic administration of A. officinarum caused a marked reduction in the body weight gain and Lee index of rats compared to the obesogenic diet-fed rats. Its administration also caused attenuation in blood pressure (systolic, diastolic, and mean), serum total cholesterol, triglyceride, and leptin, while an increase in serum HDL and adiponectin levels was noticed. The catalase and superoxide dismutase enzymatic activities were found to be remarkable in the serum of A. officinarum-treated animal groups. A. officinarum showed mild to moderate diuretic, hepatoprotective, and reno-protective effects. The A. officinarum-treated group showed less mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase while the mRNA expression of peroxisome proliferator-activated receptor and mRNA expression of cholesterol 7 alpha-hydroxylase were raised in comparison to the hypertensive group of rats evaluated by quantitative real-time polymerase chain reaction. These findings show that A. officinarum possesses antihypertensive and diuretic activities, thus providing a rationale to the medicinal use of A. officinarum in cardiovascular ailments.

Prevalence and distribution of hypertension in overweight and obese subjects in an urban community in Enugu, South East Nigeria. A post hoc analysis.

BACKGROUND: Most recent studies in Nigeria have documented high prevalence of hypertension, diabetes, and obesity. Several mechanisms may link hypertension and obesity hence the high prevalences of both disorders in Nigeria. There are however no studies on the prevalence of hypertension among the obese in urban settings. AIMS: The aim of this study was to describe the prevalence and pattern of hypertension in overweight/obese individuals in a community. METHODS: We conducted a post-hoc analysis on obese subjects 20 years and above from two urban settlements within Enugu metropolis. For database management and statistical analyses, we used the SPSS version 22. RESULTS: Data from a total of 301 individuals with obesity who met the selection criteria were re-analyzed. A total of 198 (65.8%) individuals were found to have hypertension most of whom were newly diagnosed 110 (55.6%). The prevalence of hypertension was 65.8% and increased with age and BMI. CONCLUSION: Individuals with overweight/obesity have very high rates of hypertension. The prevalence of hypertension also increased with and BMI. Thus, there is need for targeted health education in adults to address the burden of obesity and hypertension to reduce the burden of cardiovascular disease in the community.

Hypertension in Obesity: Novel Insights.

BACKGROUND: The relationship between obesity and hypertension has been established in both adults and children. The combination of obesity, hypertension and other cardiovascular risk factors significantly increases the likelihood of adverse cardiovascular effects and raises concerns about aggressive treatment strategies. OBJECTIVE: Despite the impressive elements which indicate an important role for excessive weight gain in increasing blood pressure, not all obese patients are hypertensive. A subgroup of obese people may not develop hypertension. Furthermore, masked hypertension occurs more common among obese patients, and body fat distribution has a major role in the development of hypertension. METHOD: We conducted a research of the relevant literature regarding obesity-induced hypertension and possible treatment strategies. RESULTS: Successful weight loss is correlated with blood pressure reduction and requires a multidisciplinary approach that includes personalized dietary interventions combined with regular exercise and cognitive behavioral therapy. CONCLUSION: Pharmacological therapy may be considered as part of a comprehensive obesity management strategy. More research and new treatment therapies are required in this field.

Effects of chemerin/CMKLR1 in obesity-induced hypertension and potential mechanism.

BACKGROUND: Obesity-induced hypertension (OIH) has a high morbidity and mortality, and its prevention and treatment has been a major challenge in clinical practice. Chemerin is a newly discovered adipokine closely related to OIH. METHODS: Male Wistar rats (8W) were divided into either a high-fat diet or a regular diet group. Body weight and blood pressure were measured every two weeks. After 20 weeks, serum, adipose tissue and aortic arteries were collected. Arterial tensions were detected; Immunohistochemistry, ELISA and Western blotting were used to detect the expression of chemerin, CMKLR1, Rock2 and P-MYPT1 in the aorta and perivascular adipose tissues. RESULTS: After 4 weeks, the body weight, systolic blood pressure, diastolic blood pressure and mean arterial pressure were all significantly higher in the high-fat diet group (P<0.05). There was no significant difference in serum chemerin concentration between the OIH group and the control group. However, chemerin and CMKLR1 protein expression was higher in aortic arteries and perivascular adipose tissues of the OIH group (P<0.05). The arterial tension induced by chemerin 9 (1 µM) and the expression of Rock2 and P-MYPT1 were higher in the OIH group (P<0.05). CONCLUSION: OIH positively correlated with chemerin in tissues but not serum. Arterial tension was increased by chemerin 9. Rock2/P-MYPT1 might be involved in the pathogenesis of increased vascular tone in OIH rats.

Obesity-Induced Hypertension: New Insights.

BACKGROUND: New insights on the relationship between weight loss and hypertension and the role of the newly approved anti-obesity drugs on hypertension will be discussed Methods: Weight loss is a major factor to reduce blood pressure when a patient with excess weight is advised from the health care provider to change his lifestyle. A healthy lifestyle with reduction in body weight, reduction in caloric intake, increased fruit and vegetables consumption and reduced salt intake concomitant with an increase in physical exercise can reduce body weight and hypertension in overweight and obese patients, but not all obese are able to reduce their blood pressure and lose weight without treatment and special dietary care. Moreover, most obese people lose weight for a small period and then they regain all the weight that they have lost or even worse, they increase their weight more than before starting a diet. Newly-approved weight loss drugs have variable actions on high blood pressure. Liraglutide and phentermine/topiramate seem to reduce hypertension, while after the bupropion/naltrexone or lorcaserin use trials reported a rise in blood pressure. CONCLUSION: Reduction in body weight with treatment is not always associated with reduction in obesity induced hypertension. Weight loss treatments that exhibit sympathomimetic or adrenergic actions should be used with care and for short periods of time.