Gut microbiota and fecal volatilome profile inspection in metabolically healthy and unhealthy obesity phenotypes.

BACKGROUND: People with metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) differ for the presence or absence of cardio-metabolic complications, respectively. OBJECTIVE: Based on these differences, we are interested in deepening whether these obesity phenotypes could be linked to changes in microbiota and metabolome profiles. In this respect, the overt role of microbiota taxa composition and relative metabolic profiles is not completely understood. At this aim, biochemical and nutritional parameters, fecal microbiota, metabolome and SCFA compositions were inspected in patients with MHO and MUO under a restrictive diet regimen with a daily intake ranging from 800 to 1200 kcal. METHODS: Blood, fecal samples and food questionnaires were collected from healthy controls (HC), and an obese cohort composed of both MHO and MUO patients. Most impacting biochemical/anthropometric variables from an a priori sample stratification were detected by applying a robust statistics approach useful in lowering the background noise. Bacterial taxa and volatile metabolites were assessed by qPCR and gas chromatography coupled with mass spectrometry, respectively. A targeted GC-MS analyses on SCFAs was also performed. RESULTS: Instructed to follow a controlled and restricted daily calorie intake, MHO and MUO patients showed differences in metabolic, gut microbial and volatilome signatures. Our data revealed higher quantities of specific pro-inflammatory taxa (i.e., Desulfovibrio and Prevotella genera) and lower quantities of Clostridium coccoides group in MUO subset. Higher abundances in alkane, ketone, aldehyde, and indole VOC classes together with a lower amount of butanoic acid marked the faecal MUO metabolome. CONCLUSIONS: Compared to MHO, MUO subset symptom picture is featured by specific differences in gut pro-inflammatory taxa and metabolites that could have a role in the progression to metabolically unhealthy status and developing of obesity-related cardiometabolic diseases. The approach is suitable to better explain the crosstalk existing among dysmetabolism-related inflammation, nutrient intake, lifestyle, and gut dysbiosis.

Cardiorespiratory fitness and submaximal exercise dynamics in normal-weight obesity and metabolically healthy obesity.

PURPOSE: Cardiorespiratory fitness (CRF) is critical for cardiovascular health. Normal-weight obesity (NWO) and metabolically healthy obesity (MHO) may be at increased risk for cardiovascular disease, but a comparison of CRF and submaximal exercise dynamics against rigorously defined low- and high-risk groups is lacking. METHODS: Four groups (N = 40; 10/group) based on body mass index (BMI), body fat %, and metabolic syndrome (MetS) risk factors were recruited: healthy controls (CON; BMI 18.5-24.9 kg/m2, body fat < 25% [M] or < 35% [F], 0-1 risk factors), NWO (BMI 18.5-24.9 kg/m2, body fat ≥ 25% [M] or ≥ 35% [F]), MHO (BMI > 30 kg/m2, body fat ≥ 25% [M] or ≥ 35% [F], 0-1 risk factors), or metabolically unhealthy obesity (MUO; BMI > 30 kg/m2, body fat ≥ 25% [M] or ≥ 35% [F], 2 + risk factors). All participants completed a V ˙ O2peak test on a cycle ergometer. RESULTS: V ˙ O2peak was similarly low in NWO (27.0 ± 4.8 mL/kg/min), MHO (25.4 ± 6.7 mL/kg/min) and MUO (24.6 ± 10.0 mL/kg/min) relative to CON (44.2 ± 11.0 mL/kg/min) when normalized to total body mass (p's < 0.01), and adjusting for fat mass or lean mass did not alter these results. This same differential V ˙ O2 pattern was apparent beginning at 25% of the exercise test (PGroup*Time < 0.01). CONCLUSIONS: NWO and MHO had similar peak and submaximal CRF to MUO, despite some favorable health traits. Our work adds clarity to the notion that excess adiposity hinders CRF across BMI categories. CLINICALTRIALS: gov registration: NCT05008952.

Elevated remnant cholesterol was associated with the increased metabolically unhealthy obesity risk in Chinese youth.

BACKGROUND AND OBJECTIVES: Metabolically unhealthy obesity is characterized by the presence of cardiovascular metabolic risks such as hypertension, dyslipidemia, and hyperglycemia. Research has shown a correlation between remnant cholesterol (RC) concentrations and abdominal obesity in children. However, the effect of RC concentration on metabolically unhealthy obesity remains unclear. METHODS AND STUDY DESIGN: This study included 3114 Chinese adolescents who received health check-ups. We used logistic regression models and receiver operating characteristic analysis to evaluate the correlation between RC concentration and metabolically unhealthy obesity in a cross-sectional design. RESULTS: After controlling for possible confounding variables, we found that individuals in the top and fourth quintiles of RC concentrations had a significantly higher likelihood of developing metabolically unhealthy obesity compared to those in the bottom quintile (ORs, 4.810 and 1.836; 95% CIs, 3.209-7.212 and 1.167-2.890, respectively). The risk of metabolically unhealthy obesity tended to increase with RC concentration (ptrend<0.001). In addition, boys showed positive associations between RC concentration and both BMI (r = 0.305, p<0.001) and waist circumference (r = 0.306, p<0.001). According to the analysis, the predictive accuracy of metabolically unhealthy obesity was 0.736 (95% CI, 0.690-0.781) for boys and 0.630 (95% CI, 0.573-0.687) for girls. The ideal prediction threshold was 0.66 for boys and 0.59 for girls. CONCLUSIONS: Our findings indicate that elevated RC concen-tration is linked to a higher likelihood of developing metabolically unhealthy obesity in young individuals, regardless of other known risk factors.

Dietary inflammatory index and its relationship with obesity phenotypes: a cross- sectional analysis from RaNCD cohort study.

PURPOSE: The potential dietary inflammatory index (DII) and the phenomenon of obesity have been linked in recent studies, but it is unclear whether this connection is dependent on metabolic status. Therefore, it was thought that this research would be useful in establishing the relationship between obesity phenotypes and DII. METHODS: The 5956 people who took part in the Ravansar non-communicable diseases (RaNCD) cohort research (MHNO) were put into four groups: metabolically unhealthy obesity (MUO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically healthy non-obesity. According to the International Diabetes Federation's criteria, MUO exhibits at least two metabolic disorders and have a body mass index of 30 kg/m2 or higher. DII was extracted from the participant's dietary consumption data. RESULTS: When possible confounders like age, gender, smoking, drinking alcohol, and exercise were taken into account, more adherence to DII was linked to a higher odds of MHO compared to MHNO (OR: 1.44; CI 95% 1.18, 1.75). Additionally, we discovered that greater adherence to DII was significantly related to higher odds for MUO compared to MHNO (OR: 1.67; CI 95% 1.3, 2.15). However, we found no association between adherence to DII and MUNO. CONCLUSIONS: Our findings indicated that greater adherence to DII was significantly associated with higher odds of MUO. However, it substantially increased the chances of both phenotypes of obesity. Level of evidence Level V-Cross-sectional observational study.

Adherence to the Mediterranean diet as a possible additional tool to be used for screening the metabolically unhealthy obesity (MUO) phenotype.

BACKGROUND: The terms metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) categorize subjects with obesity based on the presence or absence of cardio-metabolic risk factors. Detecting MUO phenotype is crucial due to the high risk of cardio-metabolic complications, requiring tailored and intensive follow-up. However, diagnosing MUO is time-consuming and costly. Thus, we aimed to investigate the role of Mediterranean diet (MD) in determining MHO/MUO phenotypes and whether adherence to MD could serve as an additional screening tool for MUO phenotype. METHODS: The study population of this cross-sectional observational study consisted of 275 subjects with obesity. We assessed their lifestyle habits (physical activity and smoking habits), anthropometric measurements (weight, height, waist circumference, body mass index), blood pressure, metabolic parameters, inflammatory marker (high sensitivity C reactive protein levels), adherence to MD (by PREvención con DIetaMEDiterránea (PREDIMED) questionnaire), and MHO/MUO phenotypes. RESULTS: The study included 275 individuals with obesity (256F/19M; 34.0 ± 10.5 years; BMI 38.3 ± 5.95 kg/m2). Among them, 114 (41.5%) exhibited MHO phenotype, while 161 (58.5%) had MUO phenotype. MHO phenotype exhibited favorable anthropometric and cardio-metabolic profiles, characterized by lower waist circumference (p < 0.001), BMI (p < 0.001), insulin resistance (p < 0.001), blood pressure (p < 0.001), inflammation (p < 0.001), and lipid levels (p < 0.001) compared to MUO phenotype. Notably, we found that MHO phenotype had higher adherence to MD (p < 0.001) and consumed more extra virgin olive oil (EVOO) (p < 0.001), vegetables (p < 0.001), fruits (p < 0.001), legumes (p = 0.001), fish (p < 0.001), wine (p = 0.008), and nuts (p = 0.001), while reporting lower intake of red/processed meats (p < 0.001), butter, cream, margarine (p = 0.008), soda drinks (p = 0.006), and commercial sweets (p = 0.002) compared to MUO phenotype. Adherence to MD (p < 0.001) and EVOO (p = 0.015) intake were identified as influential factors in determining the presence of MUO/MHO phenotypes. Furthermore, a PREDIMED score < 5 proved to be the most sensitive and specific cut-point value for predicting the presence of MUO phenotype (p < 0.001). CONCLUSION: High adherence to MD was associated with MHO phenotype. Moreover, we suggest that a specific cut-off of the PREDIMED score could be an indicator to discriminate patients with MUO/MHO phenotypes and therefore help in identifying patients at higher cardiovascular risk who will require specific dietary intervention.

Dietary determinants of healthy/unhealthy metabolic phenotype in individuals with normal weight or overweight/obesity: a systematic review.

Objectives: Nutritional factors are amongst the major determinants in the onset and development of obesity and metabolic complications. Nevertheless, the dietary determinants of metabolic health are not completely elucidated. The aim of this systematic review is to investigate nutritional and dietary factors that may contribute to metabolic heterogeneity in individuals with obesity or normal weight. Methods: A literature search was performed in PubMed, Scopus, EMBASE, and google scholar databases until August 2021, to locate studies that examined metabolic health and its association with intakes of specific foods or food groups, nutrient intakes or status, as well as adherence to certain dietary patterns. Two researchers had independently screened titles and abstracts, examined full-text studies, conducted data extraction, and evaluated their quality using the Newcastle-Ottawa Scale. Results: Twenty-seven studies, with a total of 39518 subjects, were included. Of these studies, 11 articles evaluated the association between different dietary patterns and metabolic phenotypes, while 15 had investigated the association of single food/nutrients intakes or nutrient status with metabolic phenotype, and one paper evaluated the association of dietary inflammatory index with metabolic health. The findings of these studies propose that healthy dietary patterns such as the Mediterranean pattern, Dietary Approaches to Stop Hypertension, and population-derived patterns (such as the "Healthy" and "Fruit and vegetable" patterns) were associated with higher odds of the metabolically healthy phenotype. Higher intakes of fruits, vegetables, dairy products, coffee/tea, vitamin D, magnesium, and flavonoids, were suggested to lower the risk of developing metabolically unhealthy phenotype, while, higher consumption of saturated fat, carbohydrate and sugar-sweetened beverages, fast foods, organ meats, and a pro-inflammatory diet increased the risk. Conclusion: Results from published studies, which were mostly cross-sectional, suggest that higher adherence to unhealthier dietary patterns, characterized by the consumption of refined and processed foods, was associated with a lower likelihood of having a healthy metabolic phenotype, while the opposite was observed for healthier dietary patterns. Findings may be used in developing nutritional strategies aimed at improving metabolic health in the population.

Ceramide d18:1/24:1 as a potential biomarker to differentiate obesity subtypes with unfavorable health outcomes.

BACKGROUND: The criteria for metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) remain controversial. This research aimed to identify a potential biomarker to differentiate the subtypes of obesity. METHODS: The study conducted a lipidomic evaluation of ceramide in the serum of 77 Chinese adults who had undergone hyperinsulinemic-euglycemic clamps. These adults were divided into three groups according to the clinical data: normal weight control group (N = 21), MHO (N = 20), and MUO (N = 36). RESULTS: The serum Cer d18:1/24:1 level in the MHO group was lower than that in the MUO group. As the Cer d18:1/24:1 level increased, insulin sensitivity decreased, and the unfavorable parameters increased in parallel. Multivariate logistic regression analysis revealed that serum Cer d18:1/24:1 levels were independently correlated with MUO in obesity. Individuals with higher levels of Cer d18:1/24:1 also had an elevated risk of cardiovascular disease. Most ceramide subtype levels increased in obesity compared to normal-weight individuals, but the levels of serum Cer d18:0/18:0 and Cer d18:1/16:0 decreased in obesity. CONCLUSIONS: The relationships between ceramide subtypes and metabolic profiles might be heterogeneous in populations with different body weights. Cer d18:1/24:1 could be a biomarker that can be used to differentiate MUO from MHO, and to better predict who will develop unfavorable health outcomes among obese individuals. TRIAL REGISTRATION: The First Affiliated Hospital of Nanjing Medical University's Institutional Review Board authorized this study protocol, and all participants provided written informed consent (2014-SR-003) prior to study entry.

Differences in metabolic characteristics between Metabolically Healthy Obesity (MHO) and Metabolically Unhealthy Obesity (MUO) in weight reduction therapy.

Metabolically Healthy Obesity (MHO) is generally recognized as the absence of any metabolic disorders and cardiovascular diseases, including type 2 diabetes, dyslipidemia, and hypertension, in obese individuals; however, it is not clearly defined. Therefore, the present study investigated differences in metabolic characteristics between individuals with MHO and Metabolically Unhealthy Obesity (MUO) during weight reduction therapy. The key factors defining MHO and the importance of weight reduction therapy for MHO were also examined. Cohort data from the Japan Obesity and Metabolic Syndrome (JOMS) study were analyzed. Subjects were divided into the MHO (n = 25) and MUO (n = 120) groups. Prior to weight reduction therapy, serum adiponectin levels were significantly higher in the MHO group than in the MUO group. Serum adiponectin levels also negatively correlated with the area of subcutaneous adipose tissue (SAT) and Homeostasis model assessment (HOMA)-R in the MHO group, but not in the MUO group. Collectively, the present results suggest the importance of adiponectin for maintaining metabolic homeostasis in the MHO group. On the other hand, no significant differences were observed in inflammatory markers between the MHO and MUO groups, suggesting the presence of chronic inflammation in both groups. Furthermore, a positive correlation was noted between changes in serum cystatin C levels and waist circumference in the MHO group, which indicated that despite the absence of metabolic disorders, the MHO group exhibited anti-inflammatory responses during weight reduction therapy. These results underscore the significance of weight reduction even for individuals with MHO.

Prevalence of liver cirrhosis based on the metabolic health and weight criteria: Report from the Korea National Health and Nutrition Examination Survey (KNHANES) data analysis.

INTRODUCTION AND OBJECTIVES: Recent studies have proposed two distinctive types of obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO), based on various physiological factors. This study sought to explore the relationship between the metabolic obesity types and the incidence of liver cirrhosis (LC) in a large nationally-representative population. MATERIALS AND METHODS: Data on 27,629 adults with MHO or MUHO, were analyzed from the Korea National Health and Nutrition Examination Survey (KNHANES) obtained from 2015 through 2019. Four categories of metabolic health and weight (MHW) were generated for analysis: (1) MHO, (2) MUHO, (3) Metabolically unhealthy normal weight (MUHNW), and (4) Metabolically healthy normal weight (MHNW). Statistical analyzes were performed with univariate and multivariate logistic regression. RESULTS: The prevalence of LC did not show statistically significant differences among the MHW categories: 0.5% in MHO, 0.4% in MUHO, 0.2% in MHNW, and 0.3% in MUHNW. The unadjusted analysis showed a significant association between self-reported LC and MUHO, but this association was not evident in the adjusted analysis. In the adjusted analysis of the prevalence of laboratory LC, a significant association emerged in the MUHO group, followed in descending order of magnitude by the MHO and MUHNW groups. A favorable fasting blood glucose level was the only factor associated with increased prevalence of reported LC in MUHO. CONCLUSIONS: The study demonstrated a difference in the prevalence of LC between MHO and MUHO. Our study concludes that the MHO phenotype is a transient status with regard to metabolic abnormalities, and caution is necessary when evaluating MHO.

Genetic Background of Metabolically Healthy and Unhealthy Obesity Phenotypes in Hungarian Adult Sample Population.

A specific phenotypic variant of obesity is metabolically healthy (MHO), which is characterized by normal blood pressure and lipid and glucose profiles, in contrast to the metabolically unhealthy variant (MUO). The genetic causes underlying the differences between these phenotypes are not yet clear. This study aims to explore the differences between MHO and MUO and the contribution of genetic factors (single nucleotide polymorphisms-SNPs) in 398 Hungarian adults (81 MHO and 317 MUO). For this investigation, an optimized genetic risk score (oGRS) was calculated using 67 SNPs (related to obesity and to lipid and glucose metabolism). Nineteen SNPs were identified whose combined effect was strongly associated with an increased risk of MUO (OR = 1.77, p < 0.001). Four of them (rs10838687 in MADD, rs693 in APOB, rs1111875 in HHEX, and rs2000813 in LIPG) significantly increased the risk of MUO (OR = 1.76, p < 0.001). Genetic risk groups based on oGRS were significantly associated with the risk of developing MUO at a younger age. We have identified a cluster of SNPs that contribute to the development of the metabolically unhealthy phenotype among Hungarian adults suffering from obesity. Our findings emphasize the significance of considering the combined effect(s) of multiple genes and SNPs in ascertaining cardiometabolic risk in obesity in future genetic screening programs.

Integrated Care Model of Adiposity-Related Chronic Diseases.

PURPOSE OF REVIEW: Although obesity is a disease, most patients with obesity do not undergo effective treatment nor adhere to long-term care. We examine the barriers that patients with obesity confront when searching for effective treatment and propose an integrated care model of adiposity-related chronic diseases in a cardio-renal metabolic unit. RECENT FINDINGS: The current care of obesity is fragmented between primary care providers, medical specialists and metabolic bariatric surgeons with little or no coordination of care between these providers. The current care of obesity heavily focuses on weight loss as the primary aim of treatment thereby reenforcing the weight stigma and turning patients away from effective therapy like metabolic bariatric surgery. An interdisciplinary cardio-renal metabolic unit that, besides weight loss, emphasizes prevention/remission of adiposity-related chronic diseases may deliver thorough and rewarding care to most patients with obesity.

Metabolically healthy versus unhealthy obese phenotypes in relation to hypertension incidence; a prospective cohort study.

BACKGROUND: Although obesity increases the risk of hypertension, the effect of obesity based on metabolic status on the incidence of hypertension is not known. This study aimed to determine the association between obesity phenotypes including metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO) and the risk of hypertension incidence. METHODS: We conducted a prospective cohort study on 6747 adults aged 35-65 from Ravansar non-communicable diseases (RaNCD) study. Obesity was defined as body mass index above 30 kg/m2 and metabolically unhealthy was considered at least two metabolic disorders based on the International Diabetes Federation criteria. Obesity phenotypes were categorized into four groups including MUO, MHO, metabolically unhealthy non obesity (MUNO), and metabolically healthy non obesity (MHNO). Cox proportional hazards regression models were applied to analyze associations with hypertension incidence. RESULTS: The MHO (HR: 1.37; 95% CI: 1.03-1.86) and MUO phenotypes (HR: 2.44; 95% CI: 1.81-3.29) were associated with higher hypertension risk compared to MHNO. In addition, MUNO phenotype was significantly associated with risk of hypertension incidence (HR: 1.65; 95% CI: 1.29-2.14). CONCLUSIONS: Both metabolically healthy and unhealthy obesity increased the risk of hypertension incidence. However, the increase in metabolically unhealthy phenotype was higher.

Transition from metabolically healthy to unhealthy overweight/obesity and risk of cardiovascular disease incidence: A systematic review and meta-analysis.

AIMS: Discrepant results have been demonstrated regarding the cardiovascular (CV) risk of populations with metabolically healthy overweight/obesity (MHO) who were transitioned into metabolically unhealthy states. So, the objective of this systematic review and meta-analysis was to estimate the risk of cardiovascular diseases (CVD) incidence in individuals with transitional MHO phenotype. DATA SYNTHESIS: A literature review was done in PubMed, Scopus, EMBASE, and google scholar databases. Pooled HRs for all fatal and nonfatal CV events were computed using random-effect models for transitional MHOs in general as well as for each sex subgroup separately. This systematic review and meta-analysis included a total of 7 prospective observational studies with a total of 7,720,165 participants, published between 2018 and 2020. The mean follow-up duration of participants was 11.7 (5.5) years. Overall, the transitional MHO individuals had a significant risk of CVD incidence [HR = 1.42, 95% CI (1.24-1.60)]. In addition, in both male and female subgroups, unstable MHO phenotype demonstrated a significant CVD risk and HRs for incident CVD in males and females were 1.51 (1.07-1.96) and 1.71 (1.08-2.34), respectively. CONCLUSION: Transition from MHO to unhealthy state throughout follow-up elevated the risk of CVD in both male and female groups. This can explain the association between MHO and incidence of CV events especially with longer follow up period. REGISTRATION CODE IN PROSPERO: CRD42021270225.

Natural course of metabolically healthy phenotype and risk of developing Cardiometabolic diseases: a three years follow-up study.

BACKGROUND: Whether the metabolically healthy obese (MHO) phenotype is a single, stable or a transitional, fluctuating state is currently unknown. The Mexican-Mestizo population has a genetic predisposition for the development of type 2 diabetes (T2D) and other cardiometabolic complications. Little is known about the natural history of metabolic health in this population. The aim of this study was to analyze the transitions over time among individuals with different degrees of metabolic health and body mass index, and evaluate the incidence of cardiometabolic outcomes according to phenotype. METHODS: The study population consisted of a metabolic syndrome cohort with at least 3 years of follow up. Participants were apparently-healthy urban Mexican adults ≥20 years with a body mass index (BMI) ≥20 kg/m2. Metabolically healthy phenotype was defined using the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) metabolic syndrome criteria and the subjects were stratified into 4 groups according to their BMI and metabolic health. For cardiometabolic outcomes we estimated the incidence of cardiometabolic outcomes and standardized them per 1, 000 person-years of follow-up. Finally, to evaluate the risk for transition and development of cardiometabolic outcomes, we fitted Cox Proportional Hazard regression models. RESULTS: Amongst the 5541 subjects, 54.2% were classified as metabolically healthy and 45.8% as unhealthy. The MHO prevalence was 39.3%. Up to a third of the population changed from their initial category to another and the higher transition rate was observed in MHO (42.9%). We also found several novel factors associated to transition to metabolically unhealthy phenotype; socioeconomic status, number of pregnancies, a high carbohydrate intake, history of obesity and consumption of sweetened beverages. Similarly, visceral adipose tissue (VAT) was a main predictor of transition; loss of VAT ≥5% was associated with reversion from metabolically unhealthy to metabolically healthy phenotype (hazard ratio (HR) 1.545, 95%CI 1.266-1.886). Finally, we observed higher incidence rates and risk of incident T2D and hypertension in the metabolically unhealthy obesity (MUHO) and metabolically unhealthy lean (MUHL) phenotypes compared to MHO. CONCLUSIONS: Metabolic health is a dynamic and continuous process, at high risk of transition to metabolically unhealthy phenotypes over time. It is imperative to establish effective processes in primary care to prevent such transitions.

Obesity, metabolic syndrome, and primary hypertension.

Primary hypertension is the dominant form of arterial hypertension in adolescents. Disturbed body composition with, among other things, increased visceral fat deposition, accelerated biological maturation, metabolic abnormalities typical for metabolic syndrome, and increased adrenergic drive constitutes the intermediary phenotype of primary hypertension. Metabolic syndrome is observed in 15-20% of adolescents with primary hypertension. These features are also typical of obesity-related hypertension. Metabolic abnormalities and metabolic syndrome are closely associated with both the severity of hypertension and the risk of target organ damage. However, even though increased body mass index is the main determinant of blood pressure in the general population, not every hypertensive adolescent is obese and not every obese patient suffers from hypertension or metabolic abnormalities typical for metabolic syndrome. Thus, the concepts of metabolically healthy obesity, normal weight metabolically unhealthy, and metabolically unhealthy obese phenotypes have been developed. The risk of hypertension and hypertensive target organ damage increases with exposure to metabolic risk factors which are determined by disturbed body composition and visceral obesity. Due to the fact that both primary hypertension and obesity-related hypertension present similar pathogenesis, the principles of treatment are the same and are focused not only on lowering blood pressure, but also on normalizing body composition and metabolic abnormalities.

Wrist circumference as a novel predictor of transition from metabolically healthy to unhealthy phenotype in overweight/obese adults: a gender-stratified 15.5-year follow-up.

BACKGROUND: Individuals with transition from metabolically healthy overweight/obese (MHO) to metabolically unhealthy overweight/obese (MUO) phenotype are significantly predisposed to greater risks of cardiovascular events compared to those with a persistent MHO phenotype. The aim of this study was to evaluate the predictive performance of wrist circumference for this transition in adults over a 15.5-year follow-up. METHODS: We included 309 males and 821 females with the age of ≥18 years old, body mass index ≥25 kg/m2, and metabolically healthy status according to the criteria of the Joint Interim Statement. The incidence of MUO phenotype was evaluated for each gender, across tertiles wrist circumference, using Cox-proportional hazard models. RESULTS: The overall rate of transition from MHO to MUO phenotype was 87.1% in males and 77.5% in females. The hazard ratios (HRs) with 95% CI across second and third tertiles of wrist circumference were 0.89 (0.64-1.24) and 1.31 (0.99-1.73) in men (P for trend =0.027); and 1.34 (1.09-1.66) and 1.61 (1.30-2.00) in women (P for trend <0.001), respectively. After multivariable adjustment, HRs across second and third tertiles of wrist circumference were 0.92 (0.64-1.32) and 1.18 (0.83-1.67) in males (p for trend =0.352), and 1.32 (1.05-1.65) and 1.34 (1.06-1.96) in females (p for trend =0.025), respectively. CONCLUSIONS: Wrist circumference significantly predicts the transition from MHO to MUO phenotype in adults of both genders. However, it is an independent predictor of the transition only in females. Future studies are warranted to clarify the role of wrist circumference mechanisms on metabolic risk deterioration.

Metabolic status is not associated with job stress in individuals with obesity: the ELSA-Brasil baseline.

PURPOSE: Job stress has proven to be a relevant cause of stress for adults, but its effect on the development of metabolic alterations in individuals with obesity is still poorly explored. We aimed to investigate the association between job stress and metabolically unhealthy obesity (MUO) phenotype in participants with obesity at the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline assessment. METHODS: This study analyzed data collected at the baseline examination between 2008 and 2010. A total of 2371 individuals with obesity were included. Two metabolic phenotypes were characterized based on the US National Health and Nutrition Examination Survey criteria. The job stress scale was based on the Brazilian version of the Swedish Demand-Control-Support Questionnaire. The association between job stress domains and MUO phenotype was assessed by binary logistic models. RESULTS: In our sample, 1297 (54.7%) participants were women, mean age was 49.6 ± 7.1 years and 1696 (71.5%) had MUO. Low skill discretion was associated with MUO after adjustment for age, sex and race. However, in fully-adjusted models, the MUO phenotype was not associated with high job demand (odds ratio [OR] = 1.05; 95% confidence interval [95%CI] 0.82-1.35), low skill discretion (OR = 1.26; 95%CI 0.95-1.68), low decision authority (OR = 0.94; 95%CI 0.70-1.25) nor low social support (OR = 0.93; 95%CI 0.71-1.20). CONCLUSION: We found a significant association between low skill discretion and an adverse metabolic profile in models adjusted for age, sex and race. No associations were significant between job stress domains and the metabolic profile of individuals with obesity in full models.

PPARγ-A Factor Linking Metabolically Unhealthy Obesity with Placental Pathologies.

Obesity is a known factor in the development of preeclampsia. This paper links adipose tissue pathologies with aberrant placental development and the resulting preeclampsia. PPARγ, a transcription factor from the ligand-activated nuclear hormone receptor family, appears to be one common aspect of both pathologies. It is the master regulator of adipogenesis in humans. At the same time, its aberrantly low activity has been observed in placental pathologies. Overweight and obesity are very serious health problems worldwide. They have negative effects on the overall mortality rate. Very importantly, they are also conducive to diseases linked to impaired placental development, including preeclampsia. More and more people in Europe are suffering from overweight (35.2%) and obesity (16%) (EUROSTAT 2021 data), some of them young women planning pregnancy. As a result, we will be increasingly encountering obese pregnant women with a considerable risk of placental development disorders, including preeclampsia. An appreciation of the mechanisms shared by these two conditions may assist in their prevention and treatment. Clearly, it should not be forgotten that health education concerning the need for a proper diet and physical activity is of utmost importance here.

METABOLOMIC ANALYSIS OF NORMAL WEIGHT, HEALTHY AND UNHEALTHY OBESITY: AMINO ACID CHANGE ACROSS THE SPECTRUM OF METABOLIC WELLBEING IN WOMEN.

Context: Obesity is a complex and heterogeneous disorder with multiple phenotypes described. Although metabolomic biomarkers of obesity have been extensively studied, biomarkers of obesity phenotypes and differences between these phenotypes and normal-weight (NW) persons have been less investigated. Objective: The objective of this cross-sectional analysis was to investigate serum amino acids (AA) as markers of metabolic alterations in obesity phenotypes and NW. Design: Cross-sectional. Subjects and Methods: By targeted metabolomics we analyzed serum samples of 70 women using ultrahigh-performance liquid chromatography/mass spectrometry. Participants were divided into 3 groups: NW, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). Results: Five AAs were significantly different between study groups: cysteine, methionine, asparagine, glutamine, and lysine (p-value <0.05 and variable importance in the projection >1). Cysteine increased linearly with metabolic unwellness from NW to MUHO. Lysine and glutamine were significantly higher, and asparagine was significantly lower in NW and MHO than in MUHO. Conclusions: By trend and group analysis we identified specific changes in serum AAs along with the progression of metabolically unwellness.

A comprehensive metabolic profiling of the metabolically healthy obesity phenotype.

BACKGROUND: The ever-increasing prevalence of obesity constitutes a major health problem worldwide. A subgroup of obese individuals has been described as "metabolically healthy obese" (MHO). In contrast to metabolically unhealthy obese (MUO), the MHO phenotype has a favorable risk profile. Despite this, the MHO phenotype is still sub-optimally characterized with respect to a comprehensive risk assessment. Our aim was to increase the understanding of metabolic alterations associated with healthy and unhealthy obesity. METHODS: In this cross-sectional study, men and women (18-70 years) with obesity (body mass index (BMI) ≥ 30 kg/m2) or normal weight (NW) (BMI ≤ 25 kg/m2) were classified with MHO (n = 9), MUO (n = 10) or NW (n = 11) according to weight, lipid profile and glycemic regulation. We characterized individuals by comprehensive metabolic profiling using a commercial available high-throughput proton NMR metabolomics platform. Plasma fatty acid profile, including short chain fatty acids, was measured using gas chromatography. RESULTS: The concentrations of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) subclasses were overall significantly higher, and high density lipoprotein (HDL) subclasses lower in MUO compared with MHO. VLDL and IDL subclasses were significantly lower and HDL subclasses were higher in NW compared with MHO. The concentration of isoleucine, leucine and valine was significantly higher in MUO compared with MHO, and the concentration phenylalanine was lower in NW subjects compared with MHO. The fatty acid profile in MHO was overall more favorable compared with MUO. CONCLUSIONS: Comprehensive metabolic profiling supports that MHO subjects have intermediate-stage cardiovascular disease risk marker profile compared with NW and MUO subjects. CLINICAL TRIAL REGISTRATION NUMBER: NCT01034436, Fatty acid quality and overweight (FO-study).