Effects of Empagliflozin Treatment on Cardiac Biomarkers in Adults With Metabolically Healthy Obesity: Results From a Randomized, Placebo-Controlled Clinical Trial.
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SUBMITTER: Khan SS
PROVIDER: S-EPMC8446809 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Identifying those parameters that could potentially predict the deterioration of metabolically healthy phenotype is a matter of debate. In this field, epigenetics, in particular DNA methylation deserves special attention. The aim of the present study was to analyze the long-term evolution of methylation patterns in a subset of metabolically healthy subjects in order to search for epigenetic markers that could predict the progression to an unhealthy state. Twenty-six CpG sites were significantly differentially methylated, both at baseline and 11-year follow-up. These sites were related to 19 genes or pseudogenes; a more in-depth analysis of the methylation sites of these genes showed that CYP2E1 had 50% of the collected CpG sites differently methylated between stable metabolically healthy obesity (MHO) and unstable MHO, followed by HLA-DRB1 (33%), ZBTB45 (16%), HOOK3 (14%), PLCZ1 (14%), SLC1A1 (12%), MUC2 (12%), ZFPM2 (12.5%) and HLA-DQB2 (8%). Pathway analysis of the selected 26 CpG sites showed enrichment in pathways linked to th1 and th2 activation, antigen presentation, allograft rejection signals and metabolic processes. Higher methylation levels in the cg20707527 (ZFPM2) could have a protective effect against the progression to unstable MHO (OR: 0.21, 95%CI (0.067-0.667), p < 0.0001), whilst higher methylation levels in cg11445109 (CYP2E1) would increase the progression to MUO; OR: 2.72, 95%CI (1.094-6.796), p < 0.0014; respectively). DNA methylation status is associated with the stability/worsening of MHO phenotype. Two potential biomarkers of the transition to an unhealthy state were identified and deserve further investigation (cg20707527 and cg11445109). Moreover, the described differences in methylation could alter immune system-related pathways, highlighting these pathways as therapeutic targets to prevent metabolic deterioration in MHO patients.
| S-EPMC8508854 | biostudies-literature
Project description:Background and aimsObesity is linked to elevated levels of inflammatory serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFa). Adiponectin and resistin are adipokines related to obesity. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of fat cells as well as systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, by following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers and adipokine profile in a Metabolically Healthy Obese (MHO) elderly population from Malaga (Andalusia, Spain).Subjetcs and methodsSubjects aged ≥65 years (65 to 87 years old) with obesity (BMI ≥30 kg/m2) were included in this study if they met ≤1 of the following criteria: systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥ 85 mmHg; triglycerides ≥150 mg/dL; HDL-C <40mg/dL in men and <50mg/dL women; and fasting blood glucose ≥100mg/dL. Selected subjects underwent a personalized intensive lifestyle modification. Anthropometric measurements, PA, MedDiet adherence, analytical parameters, and inflammatory biomarkers were analyzed after 12 months of intervention.Results166 MHO elderly subjects, 40 (24.1%) male and 126 (75.9%) female (p < 0.0001), aged 71.7±5.2 years old (65 to 87 years old) were included in the study. After 12 months of intervention, only the waist circumference was significantly reduced in all the population (-2.5 cm, p<0.0001), although weight and BMI were maintained. MedDiet adherence increased significantly (p<0.001), but all intensity levels of PA decreased significantly (p<0.001). Concerning inflammatory biomarkers, only TNFa serum increased their levels after the intervention (p<0.001). Regarding the adipokine profile, adiponectin concentrations experienced a significant increment (p<0.001); besides, resistin concentrations decreased significantly (p<0.001). In this sense, only TNFa, adiponectin, and resistin correlated with PA. Adiponectin also correlates with insulin, triglycerides and HDL-c in baseline conditions and after 12 months of intervention; CRP, IL-6, TNFa, adiponectin, and resistin concentrations correlated with anthropometric parameters and some intensities of PA. In addition, adiponectin levels correlates with insulin, triglycerides and HDL-c. In baseline conditions, resistin levels correlated positively with TNFa (p = 0.01) and CRP (p<0.0001) levels. TNFa and IL-6 correlated positively with CRP (p = 0.03 and p<0.0001, respectively). After 12 months of intervention, only IL-6 correlated positively with CRP (p = 0.006). In addition, adipokines levels correlated positively during the process of lifestyle modification. However, during this process, only IL-6 correlated positively with itself (p<0.0001) and with CRP (p = 0.03).ConclusionHealthy aging is a multifactorial biological process in which lifestyle is essential. The presence of obesity in elderly metabolically healthy population is not a problem necessarily. Elderly MHO population who eat a MedDiet and practice regularly PA are capable to modulate their production of inflammatory cytokines (CRP, IL-6, TNFa) and adipokines profile (adiponectin, resistin), preventing other metabolic disorders.
| S-EPMC9182320 | biostudies-literature
Project description:ObjectiveThe metabolically healthy obesity (MHO) phenotype is an important obesity subtype in which obesity is not accompanied by any metabolic comorbidity. However, the underlying molecular mechanisms remain elusive. In this study, a shotgun proteomics approach to identify circulating biomolecules and pathways associated with MHO was used.MethodsThe subjects were 20 African-American women: 10 MHO cases and 10 metabolically abnormal individuals with obesity (MAO) controls. Serum proteins were detected and quantified using label-free proteomics. Differential expression of proteins between the two groups was analyzed, and the list of differentially expressed proteins was analyzed to determine enriched biological pathways.ResultsTwenty proteins were differentially expressed between MHO and controls. These proteins included: hemoglobin subunits (HBA1, P = 6.00 × 10(-18) ), haptoglobin-related protein (HPR, P = 1.2 × 10(-15) ), apolipoproteins (APOB-100, P = 1.50 × 10(-40) ; APOA4, P = 1.1 × 10(-14) ), retinol-binding protein 4 (RBP4, P = 7.1 × 10(-08) ), and CRP (P = 2.0 × 10(-04) ). MHO was associated with lower levels of proinflammatory and higher levels of anti-inflammatory biomarkers when compared with MAO. Pathway analysis showed enrichment of lipids and inflammatory pathways, including LXR/RXR and FXR/RXR activation, and acute phase response signaling.ConclusionsThese findings suggested that protection from dysregulated inflammatory and lipid processes were primary molecular hallmarks of MHO. The candidate biomarkers (AHSG, RBP4, and APOA4) identified in this study are potential prognostic markers for MHO.
| S-EPMC4882259 | biostudies-literature
Project description:BackgroundMetabolic syndrome and obesity are risk factors for gallstones. However, these two factors often occur together, and few studies have focused on the association between metabolically healthy overweight/obesity (MHOW/MHO) and gallstones. We hypothesized that MHO individuals would be associated with the prevalence of gallstones.MethodsThis cross-sectional study included 125,668 participants aged 18-80 years at the Health Promotion Center of Run Run Run Shaw Hospital, Zhejiang University School of Medicine during 2017-2019 years. Each participant underwent a comprehensive health checkup. Gallstones were diagnosed by abdominal ultrasonography. Metabolically health was defined as not meeting the diagnostic criteria for metabolic syndrome (MetS). Obesity was measured by BMI. MetS and weight stratification were combined to classify the metabolism-obesity phenotypes. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% CIs.ResultsAmong 125,668 participants, 5486 (4.4%) had gallstones. 21407 (17.0%) were MHOW individuals, and 3322 (2.6%) were MHO individuals. MHOW (OR 1.40; 95%CI: 1.29-1.53) and MHO (OR 1.80; 95%CI: 1.53-2.12) participants were at higher risk of gallstones and had larger and more numerous gallstones than metabolically healthy normal weight participants. Obesity, MetS, premenopausal women and advanced age were significantly associated with the prevalence of gallstones.ConclusionsMHOW/MHO individuals exhibited a higher risk of gallstones. In metabolically healthy individuals, the risk of gallstones increased with increasing BMI. Thus, obesity was associated with the prevalence of gallstones, even in relatively metabolically healthy adults.
| S-EPMC10064513 | biostudies-literature
Project description:Although obesity is typically associated with metabolic dysfunction and cardiometabolic diseases, some people with obesity are protected from many of the adverse metabolic effects of excess body fat and are considered "metabolically healthy." However, there is no universally accepted definition of metabolically healthy obesity (MHO). Most studies define MHO as having either 0, 1, or 2 metabolic syndrome components, whereas many others define MHO using the homeostasis model assessment of insulin resistance (HOMA-IR). Therefore, numerous people reported as having MHO are not metabolically healthy, but simply have fewer metabolic abnormalities than those with metabolically unhealthy obesity (MUO). Nonetheless, a small subset of people with obesity have a normal HOMA-IR and no metabolic syndrome components. The mechanism(s) responsible for the divergent effects of obesity on metabolic health is not clear, but studies conducted in rodent models suggest that differences in adipose tissue biology in response to weight gain can cause or prevent systemic metabolic dysfunction. In this article, we review the definition, stability over time, and clinical outcomes of MHO, and discuss the potential factors that could explain differences in metabolic health in people with MHO and MUO - specifically, modifiable lifestyle factors and adipose tissue biology. Better understanding of the factors that distinguish people with MHO and MUO can produce new insights into mechanism(s) responsible for obesity-related metabolic dysfunction and disease.
| S-EPMC6763224 | biostudies-literature
Project description:When humans eat more and exercise less, they tend to become obese and unhealthy. The molecular pathways that link obesity to serious diseases like Type 2 diabetes and cardiovascular disease have become a subject of intensive scientific investigation because the exploding prevalence of obesity worldwide represents a grave new threat to the health of hundreds of millions of people. However, obesity is not always destiny. Two important clinical populations have been valuable to understand the mechanisms behind this conundrum: individuals who exhibit metabolic dysfunction, diabetes and elevated cardiovascular disease risk despite a lean body type, and individuals who are relatively protected from these dangers despite significant obesity. Study of this second group of 'metabolically healthy obese' people in particular has been revealing because such individuals exhibit specific, identifiable, anatomic, cellular and molecular features that set them apart from the rest of us who suffer declining health with increasing weight. Here, we examine some of these features, including some mouse models that are informative of mechanism, and suggest hypotheses for further study, including the possibility that genes and pathways of the immune system might offer new diagnostic or therapeutic targets.
| S-EPMC3583231 | biostudies-literature
Project description:ImportanceImproved understanding of trends in the proportion of individuals with metabolically healthy obesity (MHO) may facilitate stratification and management of obesity and inform policy efforts.ObjectivesTo characterize trends in the prevalence of MHO among US adults with obesity, overall and by sociodemographic subgroups.Design, setting, and participantsThis survey study included 20 430 adult participants from 10 National Health and Nutrition Examination Survey (NHANES) cycles between 1999-2000 and 2017-2018. The NHANES is a series of cross-sectional and nationally representative surveys of the US population conducted continuously in 2-year cycles. Data were analyzed from November 2021 to August 2022.ExposuresNational Health and Nutrition Examination Survey cycles from 1999-2000 to 2017-2018.Main outcomes and measuresMetabolically healthy obesity was defined as a body mass index of 30.0 (calculated as weight in kilograms divided by height in meters squared) without any metabolic disorders in blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), or triglycerides based on established cutoffs. Trends in the age-standardized prevalence of MHO were estimated using logistic regression analysis.ResultsThis study included 20 430 participants. Their weighted mean (SE) age was 47.1 (0.2) years; 50.8% were women, and 68.8% self-reported their race and ethnicity as non-Hispanic White. The age-standardized prevalence (95% CI) of MHO increased from 3.2% (2.6%-3.8%) in the 1999-2002 cycles to 6.6% (5.3%-7.9%) in the 2015-2018 cycles (P < .001 for trend). There were 7386 adults with obesity. Their weighted mean (SE) age was 48.0 (0.3) years, and 53.5% were women. The age-standardized proportion (95% CI) of MHO among these 7386 adults increased from 10.6% (8.8%-12.5%) in the 1999-2002 cycles to 15.0% (12.4%-17.6%) in the 2015-2018 cycles (P = .02 for trend). Substantial increases in the proportion of MHO were observed for adults aged 60 years or older, men, non-Hispanic White individuals, and those with higher income, private insurance, or class I obesity. In addition, there were significant decreases in the age-standardized prevalence (95% CI) of elevated triglycerides (from 44.9% [40.9%-48.9%] to 29.0% [25.7%-32.4%]; P < .001 for trend) and reduced HDL-C (from 51.1% [47.6%-54.6%] to 39.6% [36.3%-43.0%]; P = .006 for trend). There was also a significant increase in elevated FPG (from 49.7% [95% CI, 46.3%-53.0%] to 58.0% [54.8%-61.3%]; P < .001 for trend) but no significant change in elevated blood pressure (from 57.3% [53.9%-60.7%] to 54.0% [50.9%-57.1%]; P = .28 for trend).Conclusions and relevanceThe findings of this cross-sectional study suggest that the age-standardized proportion of MHO increased among US adults from 1999 to 2018, but differences in trends existed across sociodemographic subgroups. Effective strategies are needed to improve metabolic health status and prevent obesity-related complications in adults with obesity.
| S-EPMC9999245 | biostudies-literature
Project description:The East Asian region (China, Japan, and South Korea) is comprised of almost 1.5 billion people and recent industrialization has brought with it a pandemic of rising obesity, even in children. As these countries are rapidly aging and functioning at sub-replacement birthrates, the burgeoning costs of obesity-related care may threaten socialized healthcare systems and quality of life. However, a condition called metabolically healthy obesity (MHO) has been found to be without immediate cardiopulmonary or diabetic risk. Thus, maintenance of the MHO condition for the obese in East Asia could buffer the burden of long-term obesity care on medical systems and knowledge of the biochemical, genetic, and physiological milieu associated with it could also provide new targets for intervention. Diverse physiological, psychological, environmental, and social factors play a role in obesogenesis and the transition of MHO to a metabolically unhealthy obesity. This review will give a broad survey of the various causes of obesity and MHO, with special emphasis on the East Asian population and studies from that region.
| S-EPMC9500686 | biostudies-literature
Project description:BackgroundDespite the importance of early cardiovascular disease (CVD) intervention, little data exists for evaluating cardiovascular risk in adults without traditional CVD risk factors (e.g., diabetes, hypertension).MethodsWe included 4,544 adults from the 1999-2004 National Health and Nutrition Examination Survey without prevalent diabetes, hypertension, chronic kidney disease, or CVD. We used multi-variable adjusted Cox proportional hazards regression modeling to assess the relationship between logarithmically transformed cardiac biomarkers (high sensitivity cardiac troponin T (hs-cTnT), hs-cTnI (Abbott, Ortho, and Siemens assays), and NT-proBNP) and CVD mortality among a nationally representative cohort of relatively healthy adults.ResultsThe mean age was 38.2 years (SD 12.8) and 53.9% were women. 8.7% had elevated levels of hs-cTnT or NT-proBNP above previously established thresholds for subclinical CVD. In multivariable adjusted models, each doubling of hs-cTnT was associated with a 49% increased risk of CVD mortality (Hazard Ratio (HR) 1.49, 95%CI 1.02-2.17, p=0.04). Only two of the hs-cTnI assays (Abbott and Ortho) were significantly associated with CVD mortality (Abbott HR 1.48, 95%CI 1.06-2.07, p=0.02; Ortho HR 1.47, 95%CI 1.23-1.77, p=0.0001). Each doubling of NT-proBNP was associated with a 41% increased risk of CVD mortality (HR 1.38, 95%CI 1.09-1.74, p=0.008).ConclusionYounger patients who maintain relatively good health may still carry occult CVD risk. Efforts to reduce population-wide CVD should consider novel methods for risk stratification, as standard CVD risk factors may overlook subpopulations at risk.
| S-EPMC10705644 | biostudies-literature
Project description:BackgroundThere is a subset of individuals with overweight/obesity characterized by a lower risk of cardiometabolic complications, the so-called metabolically healthy overweight/obesity (MHOO) phenotype. Despite the relatively higher levels of subcutaneous adipose tissue and lower visceral adipose tissue observed in individuals with MHOO than individuals with metabolically unhealthy overweight/obesity (MUOO), little is known about the differences in brown adipose tissue (BAT).MethodsThis study included 53 young adults (28 women) with a body mass index (BMI) ≥25 kg/m2 which were classified as MHOO (n = 34) or MUOO (n = 19). BAT was assessed through a static 18F-FDG positron emission tomography/computed tomography scan after a 2-h personalized cooling protocol. Energy expenditure, skin temperature, and thermal perception were assessed during a standardized mixed meal test (3.5 h) and a 1-h personalized cold exposure. Body composition was assessed by dual-energy x-ray absorptiometry, energy intake was determined during an ad libitum meal test and dietary recalls, and physical activity levels were determined by a wrist-worn accelerometer.FindingsParticipants with MHOO presented higher BAT volume (+124%, P = 0.008), SUVmean (+63%, P = 0.001), and SUVpeak (+133%, P = 0.003) than MUOO, despite having similar BAT mean radiodensity (P = 0.354). In addition, individuals with MHOO exhibited marginally higher meal-induced thermogenesis (P = 0.096) and cold-induced thermogenesis (+158%, P = 0.050). Moreover, MHOO participants showed higher supraclavicular skin temperature than MUOO during the first hour of the postprandial period and during the cold exposure, while no statistically significant differences were observed in other skin temperature parameters. We observed no statistically significant differences between MHOO and MUOO in thermal perception, body composition, outdoor ambient temperature exposure, resting metabolic rate, energy intake, or physical activity levels.InterpretationAdults with MHOO present higher BAT volume and activity than MUOO. The higher meal- and cold-induced thermogenesis and cold-induced supraclavicular skin temperature are compatible with a higher BAT activity. Overall, these results suggest that BAT presence and activity might be linked to a healthier phenotype in young adults with overweight or obesity.FundingSee acknowledgments section.
| S-EPMC10808934 | biostudies-literature