Angiotensin-(1-7) and Obesity: Role in Cardiorespiratory Fitness and COVID-19 Implications.
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SUBMITTER: Motta-Santos D
PROVIDER: S-EPMC7362166 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance, which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including the SOC3 gene, which is involved in the regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow the completion of their viral replication cycles. Furthermore, a dataset using a mouse model of diet-induced obesity showed a significant increase in Ace2 expression in the lungs, which negatively correlated with the expression of genes that code for sterol response element-binding proteins 1 and 2 (SREBP). Suppression of Srebp1 showed a significant increase in Ace2 expression in the lung. Moreover, ACE2 expression in human subcutaneous adipose tissue can be regulated through changes in diet. Validation of the in silico data revealed a higher expression of ACE2, TMPRSS2 and SREBP1 in vitro in lung epithelial cells from obese subjects compared to non-obese subjects. To our knowledge this is the first study to show upregulation of ACE2 and TMPRSS2 in obesity. In silico and in vitro results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.
| S-EPMC7531362 | biostudies-literature
Project description:This study aimed to analyze the whole-blood transcriptome profile of fit children with overweight/obesity (OW/OB) compared to unfit children with OW/OB. Methods: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were evaluated. VO2peak was assessed using a gas analyzer, and participants were categorized into fit or unfit according to the CVD risk-related cut-points. Whole-blood transcriptome profile (RNA sequencing) was analyzed. Differential gene expression analysis was performed using Limma R/Bioconductor software package (analyses adjusted by sex and maturational status). Results: 256 genes were differentially expressed in fit children with OW/OB compared to unfit children with OW/OB after adjusting by sex and maturational status (FDR < 0.05). Enriched pathways analysis identified gene pathways related to inflammation (e.g., dopaminergic and GABAergic synapse pathways). Conclusion: The distinct pattern of whole-blood gene expression in fit children with OW/OB reveals genes and gene pathways that might play a role in reducing CVD risk factors later in life.
2021-08-05 | GSE164873 | GEO
Project description:ObjectiveTo investigate associations of cardiorespiratory fitness (CRF) and different measures of adiposity with cardiovascular disease (CVD) and all-cause mortality in men with known or suspected coronary heart disease (CHD).Patients and methodsWe analyzed data from 9563 men (mean age, 47.4 years) with documented or suspected CHD in the Aerobics Center Longitudinal Study (August 13, 1977, to December 30, 2002) using baseline body mass index (BMI) and CRF (quantified as the duration of a symptom-limited maximal treadmill exercise test). Waist circumference (WC) and percent body fat (BF) were measured using standard procedures.ResultsThere were 733 deaths (348 of CVD) during a mean follow-up of 13.4 years. After adjustment for age, examination year, and multiple baseline risk factors, men with low fitness had a higher risk of all-cause mortality in the BMI categories of normal weight (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.24-2.05), obese class I (HR, 1.38; 95% CI, 1.04-1.82), and obese class II/III (HR, 2.43; 95% CI, 1.55-3.80) but not overweight (HR, 1.09; 95% CI, 0.88-1.36) compared with the normal-weight and high-fitness reference group. We observed a similar pattern for WC and percent BF tertiles and for CVD mortality. Among men with high fitness, there were no significant differences in CVD and all-cause mortality risk across BMI, WC, and percent BF categories.ConclusionIn men with documented or suspected CHD, CRF greatly modifies the relation of adiposity to mortality. Using adiposity to assess mortality risk in patients with CHD may be misleading unless fitness is considered.
| S-EPMC3538467 | biostudies-literature
Project description:IntroductionCardiorespiratory fitness (CRF), as one of the most potent prognostic factors in medicine, is followed longitudinally to guide clinical management. Coronavirus disease 2019 (COVID-19) pandemic-related changes in lifestyle stand to influence CRF.ObjectiveTo assess the influence of the pandemic on perceived CRF in athlete patients and evaluate how perceived CRF change was related to demographics, pre-pandemic measured CRF, and current physical activity (PA).DesignProspective cohort study, utilizing electronic survey.SettingTertiary care sports cardiology clinical practice.ParticipantsAdult athlete patients without COVID-19 with pre-pandemic measured CRF using cardiopulmonary exercise testing.InterventionsNot applicable.Main outcome measuresPerceived change in CRF since pandemic onset; association between perceived CRF change and demographics, PA, health status, and pre-pandemic measured CRF assessed via analysis of variance (ANOVA).ResultsAmong 62 participants (male: 71%, 50.1 ± 12.1 years old), 40% (25/62) reported no change and 32% (20/62) reported an increase in perceived CRF since pandemic onset. Among the 27% (17/62) who reported a decrease in perceived CRF, in most (12/17), this was characterized as only mild. Demographics and pre-pandemic measured CRF did not differ across groups of perceived CRF change. Participants with a moderate or greater decrease in perceived CRF regarded their overall health (via Euro Quality of Life Visual Analogue Scale) as worse than other groups (ANOVA, p = .001). Although total PA was similar across groups, those who had improvement in perceived CRF reported higher levels of moderate intensity PA (ANOVA, p = .008).ConclusionsThe majority of participants perceived that they had maintained or improved CRF over the pandemic. Findings from this study suggest that a reduction in perceived CRF from pre-pandemic values in athletic patients in clinical practice may not result from population-wide pandemic changes in lifestyle. Worse health status and lower levels of moderate intensity PA were associated with perceived reduction in CRF over the pandemic in athlete patients.
| S-EPMC9088663 | biostudies-literature
Project description:Background:The interaction between cardiorespiratory fitness (CRF) and incidence of atrial fibrillation (AF) and the interaction between obesity and incidence of AF have been explored separately. Therefore, we evaluated the association between CRF, body mass index (BMI), and risk of developing AF in a cohort of middle-aged and older US Veterans. Methods:Symptom limited exercise tests (ETT) were conducted among 16,397 Veterans (97% male) from January 9,1987 to December 31,2017. No history of AF was evident at the time of the ETTs. CRF was expressed as quartiles of peak metabolic equivalents (METs) achieved within each age decile. Weight status was classified as normal (BMI < 25 kg/m2), overweight (BMI 25-30 kg/m2), obese (BMI 30-35 kg/m2), or severely obese (BMI > 35 kg/m2). Multivariable Cox proportional hazards regression models were used to compare the association between BMI, CRF categories, and incidence of AF. Results:Over a median follow-up of 10.7 years, 2,155 (13.1%) developed AF. Obese and severely obese subjects had 13% and 32% higher risks for incidence of AF, respectively, vs. normal weight subjects. Overweight and obese subjects in the most fit quartile had 50% decline in AF risk compared to the least-fit subjects. Severely obese subjects had marked increases in AF risk (~50-60%) regardless of fitness level. Risk of developing AF increases with higher BMI and lower CRF. Conclusion:Improving CRF should be advocated when assessing those at risk for developing AF.
| S-EPMC7596185 | biostudies-literature
Project description:BackgroundThe impact of cardiorespiratory fitness (CRF) and other lifestyle-related factors on severe COVID-19 risk is understudied. The present study aims to investigate lifestyle-related and socioeconomic factors as possible predictors of COVID-19, with special focus on CRF, and to further study whether these factors may attenuate obesity- and hypertension-related risks, as well as mediate associations between socioeconomic factors and severe COVID-19 risk.MethodsOut of initially 407,131 participants who participated in nationwide occupational health service screening between 1992 and 2020, n = 857 cases (70% men, mean age 49.9 years) of severe COVID-19 were identified. CRF was estimated using a sub-maximum cycle test, and other lifestyle variables were self-reported. Analyses were performed including both unmatched, n = 278,598, and sex-and age-matched, n = 3426, controls. Severe COVID-19 included hospitalization, intensive care or death due to COVID-19.ResultsPatients with more severe COVID-19 had significantly lower CRF, higher BMI, a greater presence of comorbidities and were more often daily smokers. In matched analyses, there was a graded decrease in odds for severe COVID-19 with each ml in CRF (OR = 0.98, 95% CI 0.970 to 0.998), and a two-fold increase in odds between the lowest and highest (< 32 vs. ≥ 46 ml·min-1·kg-1) CRF group. Higher BMI (per unit increase, OR = 1.09, 1.06 to 1.12), larger waist circumference (per cm, OR = 1.04, 1.02 to 1.06), daily smoking (OR = 0.60, 0.41 to 0.89) and high overall stress (OR = 1.36, 1.001 to 1.84) also remained significantly associated with severe COVID-19 risk. Obesity- and blood pressure-related risks were attenuated by adjustment for CRF and lifestyle variables. Mediation through CRF, BMI and smoking accounted for 9% to 54% of the associations between low education, low income and blue collar/low skilled occupations and severe COVID-19 risk. The results were consistent using either matched or unmatched controls.ConclusionsBoth lifestyle-related and socioeconomic factors were associated with risk of severe COVID-19. However, higher CRF attenuated the risk associated with obesity and high blood pressure, and mediated the risk associated with various socioeconomic factors. This emphasises the importance of interventions to maintain or increase CRF in the general population to strengthen the resilience to severe COVID-19, especially in high-risk individuals.
| S-EPMC8524225 | biostudies-literature
Project description:This study examined the relation between cardiorespiratory fitness (fitness) and depression symptoms prior to and during COVID-19 among adults seeking preventive medical care. Participants consisted of 967 patients attending the Cooper Clinic (Dallas, TX) pre-pandemic (March 2018-December 2019) and during the pandemic (March-December 2020). The outcome, depression symptoms, was based on the Center for Epidemiological Studies-Depression (CES-D). Maximal metabolic equivalents task (MET) levels for fitness were determined from the final treadmill speed and grade. Multiple linear regression models were computed by sex. Analysis revealed that mean fitness decreased from 11.4 METs (SD = 2.1) prior to the pandemic to 10.9 METs (SD = 2.3) during the pandemic (p-value < 0.001). The mean CES-D score increased from 2.8 (SD = 3.1) before to pandemic to 3.1 (SD = 3.2) during the pandemic (p-value = 0.003). Results from multiple linear regression indicate that increased fitness was associated with a statistically significant decrease in depression scores in men (-0.17 per MET; 95% CI -0.33, -0.02) but not women. This modest decrease may have been tempered by high fitness levels and low depression scores at baseline in this well-educated sample.
| S-EPMC9677558 | biostudies-literature
Project description:The association between diet and obesity has been widely studied and it continues to be controversial; however, the extent to which cardiorespiratory fitness (CRF) acts as a confounder or mediator in this relation has not been analyzed. The aim of this study is to examine if the relation between diet and obesity is mediated by CRF. In this cross-sectional study, fat mass (by electronic bioimpedance) was measured in 320 schoolchildren, aged 9-11 years. Diet was measured through two computerised 24-h dietary recalls and CRF was assessed by the 20-m shuttle run test. Simple mediation analyses were fitted. CRF acts as a partial mediator in the negative relationship between dietary factors (energy intake/weight, carbohydrate intake/weight, protein intake/weight, and fat intake/weight) and fat mass. The percentage of mediation ranged from 24.3 to 33.2%. Thus, Spanish schoolchildren with higher levels of energy and macronutrients intake had lower adiposity levels, especially when they had good levels of CRF.
| S-EPMC5872776 | biostudies-literature
Project description:IntroductionThe social and behavioral effects of the COVID-19 pandemic have impacted the health and physiology of most people, including those never diagnosed with COVID-19. While the impact of the pandemic has been felt across the lifespan, its effects on cardiorespiratory fitness (commonly considered a reflection of total body health) of older adults and children may be particularly profound due to social distancing and stay-at-home advisories, as well as the closure of sport facilities and non-essential businesses. The objective of this investigation was to leverage baseline data from two ongoing clinical trials to determine if cardiorespiratory fitness and body mass index were different during COVID-19 relative to before COVID-19 in older adults and children.MethodsHealthy older individuals (N = 593; 65-80 years) and 200 typically developing children (8-10 years) completed a graded maximal exercise test and had their height and weight measured.ResultsResults revealed that older adults and children tested during COVID-19 had significantly lower cardiorespiratory fitness levels than those tested before COVID-19 shutdowns (older adults: 30% lower; children: 53% lower; p's ≤ 0.001). In addition, older adults and children tested during COVID-19 had significantly higher BMI (older adults: 31.34 ± 0.57 kg/m2, p = 0.004; children: 19.27 ± 0.44 kg/m2, p = 0.05) than those tested before COVID-19 shutdowns (older adults: 29.51 ± 0.26 kg/m2, children: 18.13 ± 0.35 kg/m2). However, these differences in BMI did not remain significant when controlling for cardiorespiratory fitness.DiscussionResults from this investigation indicate that the COVID-19 pandemic, and behavior changes taken to reduce potential exposure, may have led to lower cardiorespiratory fitness levels in older adults and children, as well as higher body mass index. These findings provide relevant public health information as lower cardiorespiratory fitness levels and higher body mass indexes recorded during the pandemic could have far-reaching and protracted health consequences. Public health guidance is needed to encourage physical activity to maintain cardiorespiratory fitness and healthy body composition.Clinical trial registrationOlder adults: https://clinicaltrials.gov/ct2/show/NCT02875301, identifier: NCT02875301; Children: https://clinicaltrials.gov/ct2/show/NCT03592238, identifier: NCT03592238.
| S-EPMC9888666 | biostudies-literature
Project description:Low cardiorespiratory fitness (CRF) is associated with an increased risk of developing abdominal obesity (AO), but it is not known if and/or how changes in CRF affect AO. We examined the relationship between changes in CRF and the risk of developing AO. This is a retrospective observational study of a cohort of 1883 sedentary patients, who had participated in a clinical trial of physical activity promotion carried out in Spain (2003-2007). These data were not used in the clinical trial. At baseline, they were free of cardiovascular disease, hypertension, diabetes, dyslipidemia, and/or AO; with an indirect VO2max measurement; 19-80 years old; and 62% were women. All the measures were repeated at 6, 12, and 24 months. The exposure factor was the change in CRF at 6 or 12 months, categorized in these groups: unfit-unfit, unfit-fit, fit-unfit, and fit-fit. We considered fit and unfit participants as those with VO2max values in the high tertile, and in the moderate or low tertiles, respectively. The main outcome measure was the risk of developing AO at one and two years, as defined by waist circumference >102 (men) and >88 (women) cm. At two years, 10.5% of the participants had developed AO: 13.5% in the unfit-unfit group of change at 6 months; 10.3% in the unfit-fit group (adjusted odds ratio (AOR) 0.86; 95% confidence interval (CI) 0.49-1.52); 2.6% in the fit-unfit group (AOR 0.13; 95%CI 0.03-0.61); and 6.0% in the fit-fit group (AOR 0.47; 95%CI 0.26-0.84). Those who stayed fit at 6 months decreased the probability of developing abdominal obesity at two years.
| S-EPMC10048740 | biostudies-literature