Physical inactivity associated with NR3C1 dna hypermethylation in obesity
Introduction: obesity is a major public health issue, linked to chronic stress and metabolic dysregulation. While biological mechanisms of sedentary behavior in obesity are well known, epigenetic factors, particularly those involving the NR3C1 gene, remain unclear, especially in genes related to the regulation of chronic stress and metabolism, such as NR3C1. Objective: this study aimed to investigate the methylation profile of the NR3C1 gene in obese individuals with physical inactivity. Methods: this cross-sectional study included 119 adult volunteers with obesity (BMI ≥30) who accessed public primary health care services. Individuals using glucocorticoids were excluded. Socioeconomic, health, and lifestyle data were collected using structured questionnaires, and depressive symptoms were assessed using the Beck Depression Inventory (BDI-II). Peripheral blood samples were collected in the morning for cortisol quantification and molecular analysis of the NR3C1 gene via pyrosequencing. Multivariate Poisson regression was applied to identify factors associated with physical inactivity. Results: poisson multivariate regression analysis with robust variance showed that physical inactivity was associated with NR3C1 gene hypermethylation at CpGs 44, 45, and 46 in obese individuals and showed that physical inactivity was associated with low cortisol in the obese population. Conclusion: this study suggests an association between a sedentary lifestyle and changes in NR3C1 gene methylation in obese individuals. The association between physical inactivity and low cortisol levels strengthens the hypothesis that a sedentary lifestyle may involve epigenetic action in the dysregulation of the HPA axis of stress adaptation in obese individuals.
- Discussion
1
- 10.1113/jp279101
- Jan 1, 2020
- The Journal of Physiology
Physical inactivity and sedentary lifestyle are risk factors for obesity which may lower quality of life and increase risk for cardiovascular disease (CVD) morbidity and mortality. Obesity detrimentally alters vascular structure and function. Individuals who are obese and sedentary tend to exhibit lower capillary density. This is important because after ingesting food or exercising, obese individuals may show altered rates of skeletal muscle vasodilatation. Thus, vascular dysfunction inhibits the ability of skeletal muscles to meet metabolic demands. Metabolic supply-demand imbalances can lead to microvascular abnormalities and insulin resistance. An impaired vasodilatory response is reported in obesity and is marked by decreased nitric oxide (NO) bioavailability; there is an altered balance between NO producing enzymes (eNOS) and NO quenching enzymes ((NAD(P)Hoxidase). Imbalance between NO formation and NO quenching leads to the increase of superoxide anions that act as free radicals in the body to induce oxidative stress. Oxidative stress propagates further reduction in NO availability. While exercise has many health benefits such as improving cardiorespiratory fitness (CRF) and reducing metabolic risk factors, many individuals do not engage in a regular exercise regimen, citing ‘lack of time’ as the underlying culprit. High intensity training (HIT) is a time-effective and aerobically beneficial mode of exercise, alternative to moderate-intensity continuous training (MICT), for cardiometabolic disease risk management. However, low-volume protocols at a high-intensity have been reported as strenuous, presenting complex barriers to obese individuals. Without supervision, adherence can be low. Laboratory-based HIT protocols may not accurately mimic the applicability and feasibility of home-based HIT protocols. In an article recently published in The Journal of Physiology, Scott and colleagues evaluated the effect of a virtually supervised at-home HIT programme on muscle capillarization and muscle microvascular eNOS/NAD(P)Hoxidase ratio in obese individuals with elevated CVD risk (Scott et al. 2019). Flow-mediated dilatation (FMD) was used to assess brachial artery NO-mediated endothelial function. FMD significantly increased after HIT training, with no difference between HIT groups. Pulse wave velocity (PWV) significantly decreased after the 12-week mark in all three HIT groups, suggesting a reduction in aortic stiffness. Blood pressure (BP) remained unchanged. These data suggest that HIT training may enhance endothelial function and reduce aortic stiffness in obese adults. Obesity and lack of physical activity affect the balance between eNOS and eNOS serine1177. Immunofluorescence microscopy using cryosectioned muscle biopsy samples was used to analyse NO-producing enzymes (eNOS content and ser1177 phosphorylation) and NO quenching enzymes (NOX2 and p47phox) that critically suppresses the effect of NO. When normalized to eNOS content (eNOS ser1177/eNOs ratio), Ser1177 content levels decreased in the arterioles and capillaries with training. Terminal arteriole NOX2 content and skeletal capillary NOX2 content was significantly lower in all groups following HIT training. Increased eNOS content and reduced NOX2 content suggest an improved balance between NO synthesis and NO quenching by superoxide anion, resulting in enhanced microvascular NO bioavailability. From the image analysis using immunofluorescence microscopy, capillarization measures were quantified specific to fibres, containing at least 50 completed fibres per assessment. Capillary-to-fibre ratio, capillary-fibre perimeter exchange index and capillary contacts (number of capillaries around a fibre) were all increased by training and were all higher in type I fibres than type II fibres, with no group differences. Augmented capillarization measures may allow for an increased O2 delivery and extraction, probably contributing to the higher seen with HIT training reported by Scott et al. (2019) and throughout the literature in obese adults. GLUT4 and intramuscular triglyceride content (IMTG) were chosen as classical markers for myocyte adaptations to training. Total muscle fibre GLUT4 content was augmented following training, with a similar increase in GLUT4 content in type II fibres across the HIT groups. HIT training increased total IMGT content in all three groups, governed by an increase in lipid droplet density. Although insulin resistance is coupled with high IMGT, these results suggest that there is a greater capacity to oxidize IMGT. There is a greater efficiency of the muscle to consume fatty acids from the IMGT pool for oxidation. Increased GLUT4 coupled with increased IMGT oxidation may lead to an overall improvement in insulin sensitivity. Scott et al. (2019) eloquently demonstrated that a home-based HIT programme can effectively improve vascular function, endothelial eNOS regulation, capillarization and myocyte adaptations in obese individuals. Another noteworthy finding, less touched on by the authors, is the improvement of cardiovascular risk markers after home-based HIT intervention. Elevated BMI is associated with increased aortic stiffness (Croymans et al. 2014), a strong predictor of heart failure, kidney disease, stroke, myocardial infarction and cognitive decline; all important co-morbidities of obesity. Scott & colleagues (2019) determined that PWV was reduced after 12 weeks of HIT in obese individuals. Central aortic stiffness is mediated by many factors including arterial wall distending pressure and smooth muscle tone. Thus, reductions in aortic stiffness with exercise training may be related to improvements in endothelial function, as NO contributes to arterial compliance (Sugawara et al. 2009). Improvements in PWV may also be related to reductions in sympathetic nervous system (SNS) activity, a mechanism not explored by Scott et al. SNS activity is an important regulator of smooth muscle tone and has been shown to be elevated in the obese population (Figueroa et al. 2012). An increase in SNS activity results in vasoconstriction and increased vascular resistance, which can lead to increased aortic stiffness. Therefore, it is plausible to conclude that 12 weeks of progressive HIT training may effectively reduce SNS activity and relax smooth muscle tone, resulting in reduced PWV in obese individuals (Sugawara et al. 2009). Understanding potential mechanisms of improved vascular function with exercise is important for designing targeted interventions to improve cardiometabolic health in obesity. Scott et al. (2019) demonstrated that adherence to an at-home HIT exercise programme is achievable for obese adults. This is noteworthy, as many may think that the difficulty of exercises used in a home HIT programme such as that described by Scott et al. (2019) may deter participation. Indeed, excess body fat may limit range of motion and prevent participants from performing exercises appropriately. Moreover, jumping tasks and high impact plyometric-type movements are often thought to increase stress on joints, which could lead to orthopedic complications and musculoskeletal injury in overweight and obese adults. However, this was not case. HIT training was demonstrated to be a safe and effective exercise modality for obese adults. In summary, Scott et al. (2019) demonstrated that a home-based HIT programme aids in removing barriers to exercise and improved cardiovascular health markers in obese adults. Obese individuals can take comfort in ‘NO-ing’ that improved metabolic and vascular health is only a few weeks of clapping jumping jacks away! None declared. All authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. None declared. We'd like to acknowledge Dr Kevin Heffernan for his helpful review of this manuscript.
- Research Article
4
- 10.4103/0971-5916.184295
- Apr 1, 2016
- The Indian Journal of Medical Research
Diabetes and physical activity
- Dissertation
- 10.26174/thesis.lboro.9917687.v1
- Oct 9, 2019
Sedentary behaviour in office workers: correlates and interventions
- Research Article
- 10.18621/eurj.433962
- Nov 4, 2019
- The European Research Journal
Objectives: It is known that many different positive and negative emotions can affect appetite and also, individuals who have bipolar features often have emotional fluctuations. In this study, it was aimed to investigate the relationship between emotional appetite and bipolar features in obese individuals. Methods: One hundred and ninety obese individuals who applied for bariatric surgery and 136 non-obese individuals were evaluated with Emotional Appetite Questionnaire (EMAQ), Beck- Depression Inventory (BDI), Beck-Anxiety Inventory (BAI) and The Temperament Evaluation of Memphis, Pisa, Paris and San-Diego Auto-questionnaire (TEMPS-A) in the study. Results: In obese individuals who applied for bariatric surgery, the frequency of bipolar disorder was found to be 2% and binge eating disorder (BED) frequency was 51.2%. It was found that scores of appetite in negative emotions were higher in obese individuals with BED compared to obese individuals and it was higher in obese individuals compared to normal weight individuals. Cyclothymic features explained 27.2%, 25.8% and 15.7% of scores of appetite in negative situations of obese individuals with BED, obese individuals without BED and normal weight individuals, respectively. Conclusions: As a result of this study, it can be concluded that scores of appetite in negative situations may be affected by cyclothymic features in obese individuals with BED, in obese and normal weight individuals. Depression and anxiety symptoms are effective factors in explaining scores of appetite in negative situations of obese individuals with BED, obese and normal weight individuals.
- Research Article
485
- 10.1002/hep.32049
- Sep 1, 2021
- Hepatology (Baltimore, Md.)
Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases.
- Front Matter
37
- 10.1016/j.mayocp.2020.11.013
- Nov 24, 2020
- Mayo Clinic Proceedings
Fit Is It in COVID-19, Future Pandemics, and Overall Healthy Living
- Book Chapter
1
- 10.1007/978-3-642-21657-2_39
- Jan 1, 2011
The obesity epidemic is a major health concern. More than two thirds of Americans and more than one third of children and adolescents are overweight or obese. Physical inactivity and sedentary lifestyle are contributing factors of overweight and obesity. Increasing physical activity in overweight and obese individuals can potentially improve health status and lower the risk of major health problems. Based on the theoretical frameworks of behavioral change models, health information technologies, and pervasive interactive technologies, a conceptual model has been developed. The proposed model is an intervention method combining a behavior change model and a personalized Health IT system using an interactive accelerometer-based pervasive technology component, to increase physical activity potentially in an overweight and obese population. The accelerometer automatically synchronizes with the personal health record database over wireless networks; the decision engine utilizes the theory of planned behavior model to form a feedback; and; proper interactive feedback is provided directly to the users in the personal health record interface. A prototype was developed based on the conceptual model. The prototype measures and stores the number of steps, type of steps and caloric consumption on a daily basis with an interval of 20 minutes by an advanced accelerometer that can simply be attached to any footwear. The accelerometer synchronizes automatically the stored data with a central database as soon as the participant enters a designated wireless area. Virtual characters that are embedded inside a personal health record system convey the feedback to the users. The feedback is generated based on the theory of planned behavior decision model utilizing the stored daily physical activity data. The interface prompts knowledge-based information, presents self-monitoring trend lines, and shows virtual character changes over time such as becoming obese, to reflect the tailored feedback message. In addition, the interface is integrated in a popular social-networking website where users can review other virtual characters and generate peer pressure. The purpose of this study is to explore the feasibility of implementing a behavioral change intervention using pervasive health information technology among overweight and obese population. This research explains the development of the conceptual model, integration of wireless physical activity self-monitoring devices into personal health records, and the application of rich interactive media to convey messages to the users. The final prototype will be presented and preliminary findings will be discussed.KeywordsPhysical ActivityHealth Information TechnologyPersonal Health RecordVirtual CharacterPrevent Weight GainThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
- Research Article
- 10.1249/01.mss.0000685992.48059.3f
- Jul 1, 2020
- Medicine & Science in Sports & Exercise
PURPOSE: The leading causes of morbidity and mortality stem not from predetermined factors, but from maladaptive health behaviors that people have the ability to change. One primary example is physical inactivity, which is the fourth leading risk factor for global mortality and is a direct contributor to the global epidemic of obesity. Both the behavioral and neural mechanisms underlying sedentary behavior in healthy and obese populations are unknown, and constitute a major gap in our understanding of health behaviors. Understanding the mechanisms that regulate the motivation for exercise would allow us to devise treatments to target sedentary behaviors in both healthy and obese populations. As a precursor for these studies, the purpose here was to delineate levels of exercise motivation in both humans and a preclinical mouse model of obesity. METHODS: Self-reported measurements of exercise motivation in humans (n=727) was collected via Amazon Mechanical Turk. Voluntary wheel running data was collected in both wild type mice and mice with a targeted deletion of the basic helix-loop-helix (bHLH) gene Nhlh2 (N2KO), which serve as a preclinical model of obesity. Wheel running data was collected continuously for a period of 21 days as well as after a 72-hour period of wheel deprivation (rebound running response, Basso & Morrell, 2015). RESULTS: Here, we demonstrate that compared to normal weight controls, exercise motivation is significantly impaired in obese individuals, with normal weight controls reporting higher intrinsically regulated motivations to exercise, and obese individuals reporting higher externally regulated motivations to exercise. Further, we demonstrate that wheel running in rodents is highly motivating and that running motivation is significantly impaired in the N2KO mice. CONCLUSIONS: Impairments in exercise motivation may be a driver of obese outcomes, which are demonstrated here in both human and preclinical models of obesity. Previous work from our lab has demonstrated that regions of the motivational circuitry including the medial prefrontal cortex regulate the motivation for voluntary wheel running in rodents. We are currently investigating in both wild type and N2KO mice the hypothesis that neural activity in the PFC, modulated by dopamine, regulates the motivation for exercise.
- Research Article
180
- 10.1016/j.clnesp.2022.06.001
- Aug 1, 2022
- Clinical Nutrition ESPEN
Sedentary behavior and physical inactivity may increase the risk of obesity. This systematic review and meta-analysis aimed to investigate: i) the prevalence/incidence of sedentary behavior and physical inactivity, ii) the association of sedentary behavior and physical inactivity with obesity, and iii) the objective and subjective measures, diagnostic criteria, and cut-off points to estimate sedentary behavior and physical inactivity in adults and older adults with obesity. We conducted a systematic review and meta-analysis in PubMed, Scielo, Lilacs, and Cochrane Library databases. A meta-analysis of a random-effects model was performed to estimate the combined prevalence of sedentary behavior and physical inactivity and their association with obesity. Twenty-three studies involving 638,000 adults and older adults were included in the systematic review. A meta-analysis was conducted with 111,851 individuals with obesity. The combined prevalence of sedentary behavior was 31% (95% CI, 23-41%), and physical inactivity was 43% (95% CI, 31-55%). Significant associations between obesity and sedentary behavior (OR 1.45, 95% CI, 1.21-1.75) and physical inactivity (OR 1.52, 95% CI, 1.23-1.87) were found. Nine studies have used objective measures to assess physical activity levels, such as accelerometers and pedometers, whereas fourteen applied subjective methods and self-reported questionnaires. As expected, we found elevated rates of sedentary behavior and physical inactivity in individuals with obesity and a positive risk association. The wide range of objective and subjective measures, methods and cut-offs resulted in great variations of physical inactivity and sedentary behavior estimates. PROSPERO (CRD42016037747).
- Research Article
33
- 10.1108/11766091011094527
- Nov 23, 2010
- Qualitative Research in Accounting & Management
PurposeThere is a growing interest in research focusing on performance management practices in the public sector, but research is still limited with regards to public primary healthcare services (PHSs), which play an important role in national healthcare systems. These organisations are frequently criticised for alleged poor performance management practices and misuse of resources, though such claims are not always substantiated. The purpose of this study is to examine performance management practices in public PHSs.Design/methodology/approachThree case studies of PHSs organisations were conducted resulting in interview material and archival data. Otley's performance management framework was used to examine the data.FindingsIt is found that the performance management systems of the studied PHSs were disjoint and lacked consistency and coherence. Lack of direction and motivational were key issues in PHSs. Furthermore, the observations indicate that vertical controls between PHSs and parent organisation were weak and accountability poor.Research limitations/implicationsGeneralisability of findings and social desirability bias are the important limitations. A key research implication is that the conceptual framework adopted can be meaningfully used to generate insights into performance management issues in public sector healthcare organisations.Practical implicationsThe study highlights the implications of the poor design and use of performance management systems and highlights areas for improvement in the organisations studied, and potentially across the sector.Originality/valueThis study is the first to draw upon Otley's performance management framework to examine performance management practices in PHSs and to demonstrate its usefulness in this context.
- Research Article
3
- 10.1111/scs.12896
- Aug 2, 2020
- Scandinavian Journal of Caring Sciences
Frequent attendance is largely a temporary phenomenon, but only few previous studies have made a distinction between long-term frequent attenders (FAs) and short-term FAs. The aim of this study is to compare the characteristics of middle-aged long-term FAs and short-term FAs. Data from a large Northern Finland Birth Cohort 1966 study's (NFBC1966) 46-year follow-up study (performed in 2012, N=10321) were used. The participants (n=4390) had used public primary healthcare (PPHC) services at least once during 2013-2016 according to Finnish national register data on outpatient visits. A FA was considered a patient who had used PPHC services ≥8 times during 1year. A long-term FA: a patient who was a FA in at least 3years during 2013-2016. A short-term FA: a patient who was a FA in 1 or 2years in 2013-2016. Cross-tabulation, Pearson's chi-squared test, Mann-Whitney U test, and univariate and multivariate binary logistic regression analyses were used. Of the 4390 participants, 132 (3.0%) were long-term FAs, 645 (14.7%) were short-term FAs, and 3613 (82.3%) were non-FAs. During 2013-2016, long-term FAs accounted for 34.8% of PPHC visits, while short-term FAs accounted 15.4%. Compared to short-term FAs, depression and high income (preventive attribute) were associated with long-term FAs. Female gender and managing usual activities were associated with short-term FAs. Poor self-reported health was associated with both long-term FAs and short-term FAs but increased the risk of being a long-term FA over three times compared to short-term FAs. Middle-aged long-term FAs and short-term FAs have distinct characteristics; namely, depression and high income differentiate long-term FAs from short-term FAs. Poor self-reported health was associated with long-term FAs in particular. In order to identify FAs with prolonged service needs and to develop far-reaching interventions, the focus of research should be on long-term FAs.
- Research Article
- 10.3389/frai.2025.1538807
- Jun 18, 2025
- Frontiers in artificial intelligence
The rapid advancement of technology has brought numerous benefits to public health but has also contributed to a rise in sedentary lifestyles, linked to various health issues. As prolonged inactivity becomes a growing public health concern, researchers are increasingly utilizing machine learning (ML) techniques to examine and understand these patterns. ML offers powerful tools for analyzing large datasets and identifying trends in physical activity and inactivity, generating insights that can support effective interventions. This review aims to: (i) examine the role of ML in analyzing sedentary patterns, (ii) explore how different ML techniques can be optimized to improve the accuracy of predicting sedentary behavior, and (iii) assess strategies to enhance the effectiveness of ML algorithms. A comprehensive search was conducted in PubMed and Scopus, targeting peer-reviewed articles published between 2004 and 2024. The search included the subject terms "sedentary behavior," "sedentary lifestyle health," and "machine learning sedentary lifestyle," combined with the keywords "physical inactivity" and "diseases" using Boolean operators (AND, OR). Articles were included if they addressed the health impacts of sedentary behavior or employed ML techniques for its analysis. Exclusion criteria involved studies older than 20 years or lacking direct relevance. After screening 33 core articles and identifying 13 more through citation tracking, 46 articles were included in the final review. This narrative review describes the characteristics of sedentary behavior, associated health risks, and the applications of ML in this context. Based on the reviewed literature, sedentary behavior was consistently associated with cardiovascular disease, metabolic disorders, and mental health conditions. The review highlights the utility of various ML approaches in classifying activity levels and significantly improving the prediction of sedentary behavior, offering a promising approach to address this widespread health issue. ML algorithms, including supervised and unsupervised models, show great potential in accurately detecting and predicting sedentary behavior. When integrated with wearable sensor data and validated in real-world settings, these models can enhance the scalability and precision of AI-driven interventions. Such advancements support personalized health strategies and could help lower healthcare costs linked to physical inactivity, ultimately improving public health outcomes.
- Research Article
1
- 10.1016/j.eurpsy.2016.01.191
- Mar 1, 2016
- European Psychiatry
Unhealthy behaviours and mental health among Italian adolescents
- Research Article
6
- 10.1016/j.pcd.2014.09.006
- Oct 18, 2014
- Primary Care Diabetes
Lifestyle of metabolically healthy obese individuals
- Research Article
188
- 10.1001/archpedi.162.8.756
- Aug 1, 2008
- Archives of Pediatrics & Adolescent Medicine
To examine the prevalence and correlates of physical inactivity and sedentary behavior among immigrant and US-born children. Cross-sectional analysis using data from the 2003 National Survey of Children's Health, a telephone survey conducted between January 29, 2003, and July 1, 2004. United States. Multivariate logistic and least squares regression models were used to analyze immigrant differentials among 68 288 children aged 6 through 17 years. Main Exposure Ethnic-immigrant status. Prevalence and odds of regular physical activity, inactivity, television watching, and lack of sports participation. Physical inactivity and sedentary behaviors varied widely among children in various ethnic-immigrant groups. For example, 22.5% of immigrant Hispanic children were physically inactive compared with 9.5% of US-born white children with US-born parents. Approximately 67% of immigrant Hispanic children did not participate in sports compared with 30.2% of native Asian children. Overall, immigrant children were significantly more likely to be physically inactive and less likely to participate in sports than native children; they were, however, less likely to watch television 3 or more hours per day than native children, although the nativity gap narrowed with increasing acculturation levels. Compared with native white children, the adjusted odds of physical inactivity and lack of sports participation were both 2 times higher for immigrant Hispanic children with foreign-born parents, and the odds of television watching were 1.5 and 2.3 times higher for native Hispanic and black children, respectively. Immigrant children in each ethnic minority group generally had higher physical inactivity and lower sports participation levels than native children. To reduce disparities, health education programs need to promote physical activity among children in immigrant families.
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