Phenotyping obesity: A focus on metabolically healthy obesity and metabolically unhealthy normal weight.

Over the past 4 decades, research has shown that having a normal body weight does not automatically imply preserved metabolic health and a considerable number of lean individuals harbour metabolic abnormalities typically associated with obesity. Conversely, excess adiposity does not always equate with an abnormal metabolic profile. In fact, evidence exists for the presence of a metabolically unhealthy normal weight (MUHNW) and a metabolically healthy obese (MHO) phenotype. It has become increasingly recognised that different fat depots exert different effects on the metabolic profile of each individual by virtue of their location, structure and function, giving rise to these different body composition phenotypes. Furthermore, other factors have been implicated in the aetiopathogenesis of the body composition phenotypes, including genetics, ethnicity, age and lifestyle/behavioural factors. Even though to date both MHO and MUHNW have been widely investigated and documented in the literature, studies report different outcomes on long-term cardiometabolic morbidity and mortality. Future large-scale, observational and population-based studies are required for better profiling of these phenotypes as well as to further elucidate the pathophysiological role of the adipocyte in the onset of metabolic disorders to allow for better risk stratification and a personalised treatment paradigm.

Physical activity in relation to metabolic health and obesity: The Feel4Diabetes study.

AIM: To examine physical activity levels in association with metabolic health and estimate the stability of metabolically healthy obese (MHO) phenotypes over a 2-year period. METHODS: In total, 2848 men and women from families at risk of the development of diabetes were recruited. Participants were classified as obese or non-obese and metabolic health was defined using five existing definitions. Physical activity was estimated with the International Physical Activity Questionnaire and pedometers. RESULTS: Prevalence of the MHO phenotype varied among definitions (0% to 20.2%). Overall, the MHO were more active than the metabolically unhealthy obese (MUO). Daily sitting hours (odds ratio [OR] = 1.055, 95% confidence interval [CI]: 1.009-1.104) and daily steps (per 500; OR = 0.934, 95% CI: 0.896-0.973) were remarkable predictors of metabolic health in individuals with obesity; and likewise, in individuals without obesity. After 2 years, 44.1% of baseline MHO adults transitioned to MUO, while 84.0% of the MUO at baseline remained at the same phenotype. Although physical activity was not a major determinant in phenotype transitioning, daily steps were associated with the maintenance of metabolic health over time in the non-obese group. CONCLUSION: A universally accepted definition for MHO is needed. Being physically active can contribute to a metabolically healthy profile even in the presence of obesity; still, MHO is a transient condition and physical activity alone may not be an adequate factor for its maintenance.

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.

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.

Maternal hyperoxygenation during pregnancy as a tool in fetal disease diagnosis and treatment.

Maternal hyperoxygenation (MHO) consists of giving pregnant women (60% to 100%) oxygen through a facemask and using ultrasound assess or monitor the influence on fetal cardiovascular circulation. This review discusses the findings and the utility of acute and chronic MHO in various fetal diseases.

Israeli soldiers' intentions and actions toward seeking mental health help: Barriers and facilitators.

BACKGROUND: While military settings may increase psychological distress, soldiers frequently avoid seeking professional help. This study aimed to examine barriers and facilitators associated with intentions to seek help and actually seeking help from a mental health officer (MHO) and how these differ among soldiers who had sought help in the past and those who had not. METHOD: This cross-sectional study included 263 combat and noncombat soldiers. The Health Belief Model and the Help-Seeking Model were the theoretical framework used to map the potential variables associated with soldiers' decision to seek help. RESULTS: Stigma and administrative barriers were found to be significant barriers to both the intention to seek help and actually consulting an MHO. These findings were more definitive among combat soldiers. The belief in the effectiveness of mental health treatment was positively associated with the intention to seek help. Positive associations were found between well-being, perceived seriousness of one's condition, and belief in the effectiveness of mental health care and intention to seek MHO help. Distress and self-concealment were positively associated with actual consultation with an MHO. Public stigma about seeking help was associated with both the intention to seek mental health assistance and actually consulting an MHO. CONCLUSION: Military commanders should make an effort to make soldiers feel safe to seek mental health assistance by creating a supportive organizational atmosphere to reduce the stigma associated with mental health care.

Obesity Without Metabolic Abnormality and Incident CKD: A Population-Based British Cohort Study.

RATIONALE & OBJECTIVE: Metabolically healthy obesity (obesity without any metabolic abnormality) is not considered to be associated with increased risk of morbidity and mortality. We examined and quantified the association between metabolically healthy overweight/obesity and the risk of incident chronic kidney disease (CKD) in a British primary care population. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: 4,447,955 of the 5,182,908 adults in The Health Improvement Network (THIN) database (United Kingdom, 1995-2015) with a recorded body mass index (BMI) at the time of registration date who were free of CKD and cardiovascular disease. EXPOSURE: 11 body size phenotypes were created, defined by BMI categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and dyslipidemia). OUTCOME: Incident CKD defined as a recorded code for kidney replacement therapy, a recorded diagnosis of CKD, or by an estimated glomerular filtration rate of<60mL/min/1.73m2 for≥90 days, or a urinary albumin-creatinine ratio>3mg/mmol for≥90 days. RESULTS: Of the 4.5 million individuals, 1,040,921 (23.4%) and 588,909 (13.2%) had metabolically healthy overweight and metabolically healthy obesity, respectively. During a mean follow-up interval of 5.4±4.3 (SD) years, compared with individuals with a metabolically healthy normal weight (n=1,656,231), there was a higher risk of incident CKD among those who had metabolically healthy overweight (adjusted HR, 1.30 [95% CI, 1.28-1.33]) and metabolically healthy obesity (adjusted HR, 1.66 [95% CI, 1.62-1.70]). The association was stronger in those younger than 65 years of age. In all BMI categories, there was greater risk of incident CKD with a greater number of metabolic abnormalities in a graded manner. LIMITATIONS: Potential misclassification of metabolic status due to delayed diagnosis and residual confounding due to unmeasured factors. CONCLUSIONS: Overweight and obesity without metabolic abnormality are associated with a higher risk of incident CKD compared with those with normal body weight and no metabolic abnormality.

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.

Antiapoptotic activity of methyl (3R,4E,6Z,15E)-3-hydroxyoctadecatrienoate in human cervical carcinoma HeLa cells.

Inhibitors of thapsigargin-induced cell death in human cervical carcinoma HeLa cells were screened among the metabolites of marine organisms. The MeOH extract of the cyanobacterium Rivularia sp. was found to exhibit inhibitory activity. Column chromatography purification was used to isolate methyl (3R,4E,6Z,15E)-3-hydroxyoctadecatrienoate (MHO) as the active compound. MHO was determined to inhibit apoptotic stimuli-induced cell death in HeLa cells.

Metabolically healthy obesity is associated with longitudinal changes in high-density lipoprotein cholesterol in Chinese adults.

PURPOSE: Whether metabolically healthy obesity (MHO) is associated with longitudinal changes in high-density lipoprotein cholesterol (HDL-C) remains unclear. METHODS: MHO was defined as participants with overweight and obesity (BMI ≥ 24.0 kg/m2, n = 2921), free of history of metabolic diseases, and without abnormalities of blood pressure, fasting blood glucose, hemoglobin A1c, lipid profile, carotid artery and liver ultrasonographic findings at baseline. Metabolically healthy normal weight (MHN) was defined as participants with normal weight (BMI < 24.0 kg/m2, n = 9578) and without above-mentioned abnormalities. HDL-C, fasting blood glucose, hemoglobin A1c, and blood pressure were assessed annually. Glucose abnormality was considered if either FBG ≥ 5.6 mmol/L or HbA1c ≥ 5.7%; while, high blood pressure (HBP) was considered if either systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 80 mmHg during 5 years of follow-up. RESULTS: Compared with the MHN group, the adjusted mean difference in HDL-C change rate was - 0.005 mmol/L per year [95% confidence interval (CI) - 0.007, - 0.003] for MHO after adjustment for a series of potential confounders. Furthermore, transiting to abnormality of blood glucose, but not high blood pressure, was associated with lower cumulative average of HDL-C in MHN group, compared with those remained in metabolically healthy status. CONCLUSIONS: MHO and transiting from metabolically healthy to abnormality of blood glucose were associated with HDL-C in Chinese adults. LEVEL OF EVIDENCE: III, cohort study.

Metabolic abnormalities, but not obesity per se, associated with chronic kidney disease in a Taiwanese population.

BACKGROUND AND AIMS: It is inconclusive whether obesity itself or metabolic abnormalities are linked to chronic kidney disease (CKD). The aim of this study was to examine the association between different subtypes of obesity and metabolic abnormalities with CKD in adults. METHODS AND RESULTS: This study enrolled 14,983 eligible subjects stratified into metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obesity (MUO) according to body mass index and metabolic syndrome status (ATP-III criteria). The metabolic healthy phenotype was defined as the absence of both metabolic syndrome and any known diabetes, coronary artery disease, stroke, hypertension or dyslipidemia. Early and advanced CKD were defined as eGFR<60, proteinuria, or structural abnormalities as detected by renal sonography. The prevalence of CKD was 2.5, 3.0, 4.0, 10.6, 9.5, and 10.5% in subjects with MHNW, MHOW, MHO, MUNW, MUOW, and MUO, respectively. In the multivariate analysis, the MUNW (OR:2.22, P < 0.001), MUOW (OR:2.22, P < 0.001), and MUO (OR:2.45, P < 0.001) groups were associated with early CKD. For advanced CKD, the OR was 2.56 (P < 0.001), 2.31 (P < 0.001), and 3.49 (P < 0.001) in the MUNW, MUOW, and MUO groups, respectively. The associated risks of early and advanced CKD were not significant in the MHOW and MHO group. MUOW and MUO were associated with higher risk of CKD compared with MHOW and MHO after adjusting other variables. CONCLUSIONS: Metabolic abnormalities, but neither overweight nor obesity, were associated with a higher risk of CKD in adults.

Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise in many countries, paralleling the epidemic of obesity worldwide. In the last years, the concept of metabolically healthy obesity [MHO, generally defined as obesity without metabolic syndrome (MetS)] has raised considerable scientific interest. MHO is a complex phenotype with risks intermediate between metabolically healthy individuals with normal-weight (NWMH) and patients who are obese and metabolically unhealthy (MUO, i.e. obesity with MetS). In this review we aimed to examine the association and pathophysiological link of NAFLD with MHO and MUO. Compared to NWMH individuals, patients with obesity, regardless of the presence of MetS features, are at higher risk of all-cause mortality and cardiovascular events. Moreover, MHO patients have a greater risk of NAFLD development and progression compared to NWMH individuals. However, this risk is generally lower than that of MUO patients, suggesting a stronger adverse effect of coexisting MetS disorders than obesity per se on the severity of NAFLD. Nevertheless, since MHO is a dynamic state (with a significant proportion of MHO subjects progressing to MUO over time) and NAFLD itself may predict the transition from MHO to MUO, we believe that any effort should be made to identify NAFLD in all obese individuals, although they appear to be "metabolically healthy". Future research is needed to better understand the role of NAFLD and other pathogenic factors potentially involved in the transition from MHO to MUO and to elucidate how this transition may affect the presence and severity of NAFLD.

Toxicity, Pharmacokinetics, and Gut Microbiome of Oral Administration of Sesterterpene MHO7 Derived from a Marine Fungus.

Sesterterpene MHO7 derived from mangrove fungus is a novel estrogen receptor degrader for the treatment of breast cancer. To explore its safety and pharmacokinetics in vivo, Log P/D values, stability in simulated gastric/intestinal (SGF/SIF), toxicity, and pharmacokinetics studies were carried mainly by liquid chromatography technique coupled with tandem mass spectrometry (LC-MS/MS) method in mice, and the effect of MHO7 on mice gut microbiota at different time points was revealed by 16S rRNA sequencing. Log P/D values ranged 0.93-2.48, and the compound in SGF and SIF is stable under the concentration of 5 mM·L-1. The maximum tolerance dose (MTD) of oral administration in mice was 2400 mg·kg-1. The main pharmacokinetics parameters were as following: Cmax of 1.38 µg·mL-1, Tmax of 8 h, a half-life (t1/2) of 6.97 h, an apparent volume of mean residual time (MRT) of 8.76 h, and an area under the curve (AUC) of 10.50 h·µg·mL-1. MHO7 displayed a wide tissue distribution in mice, with most of the compound in liver (3.01 ± 1.53 µg·g-1) at 1 h, then in fat (5.20 ± 3.47 µg·g-1) at 4 h, and followed by reproductive organs with the concentrations of 23.90 ± 11.33 µg·g-1,13.69 ± 10.29 µg·g-1, 1.46 ± 1.23 µg·g-1, and 0.36 ± 0.46 µg·g-1 at 8, 12, 20 and 30 h, respectively. The most influenced genera of gut microbiome belonged to phylum Firmicutes (21 of 28), among which 18 genera originated from the order Clostridiales, class Clostridia, and families of Ruminococcaceae (11 of 18) and Lachnospiraceae (4 of 18). These results provide that MHO7 is suitable for oral administration in the treatment of breast cancer with the target organs of reproductive organs and regulation on Ruminococcaceae and Lachnospiraceae.

Effects of low-fat compared with high-fat diet on cardiometabolic indicators in people with overweight and obesity without overt metabolic disturbance: a systematic review and meta-analysis of randomised controlled trials.

Randomised controlled trials comparing low- v. high-fat diets on cardiometabolic risk factors in people with overweight or obesity have shown inconsistent results, which may be due to the mixed metabolic status of people with excess adiposity. The role of dietary fat manipulation in modifying cardiometabolic indicators in people with overweight or obese without metabolic disturbance is unclear. Thus, meta-analysis was conducted to compare low- v. high-fat diets on cardiometabolic indicators in people who are overweight or obese without metabolic disturbance in the present study. Databases were searched until October 2016. The pooled effects of outcomes with heterogeneity were calculated with a random-effects model, heterogeneities were analysed by subgroup and meta-regression. As a result, twenty studies with 2106 participants were included in the meta-analysis. Total cholesterol and LDL-cholesterol levels were lower following low-fat diets compared with high-fat diets: weighted mean difference (WMD) was -7·05 mg/dl (-0·18 mmol/l; 95 % CI -11·30, -2·80; P=0·001) and -4·41 mg/dl (-0·11 mmol/l; 95 % CI -7·81, -1·00; P=0·011), respectively. Conversely, significant higher level of TAG (WMD: 11·68 mg/dl (0·13 mmol/l), 95 % CI 5·90, 17·45; P<0·001) and lower level of HDL-cholesterol (WMD: -2·57 mg/dl (-0·07 mmol/l); 95 % CI -3·85, -1·28; P<0·001) were found following low-fat diets compared with high-fat diets. In conclusion, dietary fat manipulation has a significant influence on blood lipid levels in people with overweight or obesity without metabolic disturbances.

Effect of Different Obesity Phenotypes on Incidence of Chronic Kidney Disease in Tehranian Adults.

BACKGROUND: The aim of this community-based study is to ascertain the effect of different obesity phenotypes on the incidence of chronic kidney disease in Iranian adults. STUDY DESIGN: A prospective cohort study, the Tehran Lipid Glucose Study (TLGS). SETTING AND PARTICIPANTS: Adults aged ≥ 20 years with a mean age of 40.38 years (54.8% female) who were free from chronic kidney disease (CKD) at baseline (phase 1) and were followed up at 3 time stages (phases 2, 3, and 4) for a mean duration of 9.4 years to assess the risk for CKD. PREDICTOR: Obesity phenotypes. OUTCOME: Incidence of chronic kidney disease. MEASUREMENTS: Glomerular filtration rate (GFR) was estimated from the simplified equation developed using data from the Modification of Diet in Renal Disease (MDRD) Study. RESULTS: CKD events occurred in 1162 participants. The prevalence of the 2 known obesity phenotypes (metabolically obese normal weight [MONW] and metabolically healthy but obese [MHO]) in the overall population was 3.5% and 8.8%, respectively. According to Kaplan-Meier curves, rates of freedom from CKD in the MHO and MONW obesity phenotypes were 75.3% and 60.6%, respectively (p < 0.0001). Age- and sex-adjusted (model 1) hazard ratios for participants with MHO or MONW obesity phenotype were 1.14 (95% confidence interval [CI], 0.91-1.43) and 1.43 (95% CI, 1.09-1.88), respectively. After further adjustment for confounder variables (model 2), multivariate-adjusted hazard ratios for CKD for participants with MHO or MONW obesity phenotypes were 1.23 (95% CI, 0.93-1.62) and 1.43 (95% CI, 1.08-1.90), respectively. CONCLUSION: Adults with the MONW obesity phenotype compared to those with MHO obesity phenotype have a higher risk for incidence of CKD. The results indicate that having a normal weight is not the only factor to protect against incidence of CKD.

Obesity, metabolic abnormality, and health-related quality of life by gender: a cross-sectional study in Korean adults.

PURPOSE: This study sought to compare the association between health-related quality of life (HRQoL) and four body health types by gender. METHODS: The study included 6217 men and 8243 women over 30 years of age chosen from a population-based survey. Participants were grouped by body mass index and metabolic abnormality into four types: metabolically healthy normal weight, metabolically abnormal but normal weight (MANW), metabolically healthy obesity (MHO), and metabolically abnormal obesity (MAO). HRQoL was measured using the EQ-5D health questionnaire. The outcomes encompassed five dimensions (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression), and the impaired HRQoL dichotomized by the EQ-5D preference score. Complex sample multivariate binary logistic regression analyses were conducted to adjust for sociodemographic variables, lifestyle factors, and disease comorbidity. RESULTS: Among men, those in the MANW group presented worse conditions on all dimensions and the impaired HRQoL compared to other men. However, no significant effect remained after adjusting for relevant covariates. For women, those in the MAO group had the most adversely affected HRQoL followed by those females in the MHO group. The domain of mobility and impaired HRQoL variable of the MAO and MHO groups remained significant when controlling for all covariates in the model. CONCLUSIONS: The MANW is the least favorable condition of HRQoL for men, suggesting that metabolic health may associate with HRQoL more than obesity for males. In women, the MAO and MHO groups had the most adversely affected HRQoL, implying that MHO is not a favorable health condition and that obesity, in general, may be strongly associated with HRQoL in women.

Prevalent hyperglycemia in older obese population and age-dependent convergence of obese indices: Results of a cross-sectional study of Japanese generations over the adult life span.

PURPOSE/AIM: An age-dependent decline has been observed in the association between obesity and type 2 diabetes, a major comorbidity of obesity, although the evidence is limited. Therefore, we investigated the association and the plausible underlying mechanism in a large epidemiological study. MATERIALS AND METHODS: We examined the association between the degree of obesity and hyperglycemia in five age groups (20-39, 40-49, 50-59, 60-69, and 70-85 years) in a cross-sectional study of 78,776 apparently healthy Japanese men and women who underwent a checkup in 2012. Hyperglycemia was defined as glycosylated hemoglobin (HbA1c) of ≥5.7% and/or pharmacotherapy for diabetes. RESULTS: The incidence of hyperglycemia was three times higher in the 70-85-year-old group (62%) than in the 20-39-year-old group (20%) in obese individuals (body mass index [BMI] ≥ 27.0 kg/m(2)). However, the incidence was 12 times higher in reference-weight individuals (21.0-22.9 kg/m(2); 48% and 4%, respectively). As age increased, mean BMI and waist circumference approached certain non-obese ranges (22-24 kg/m(2) and 80-86 cm, respectively), even in hyperglycemic subjects. Logistic regression analysis revealed an age-dependent decline in the association between obesity and hyperglycemia, relative to that in reference-weight individuals. CONCLUSIONS: Our results confirmed the previously reported age-dependent decline in the association between obesity and hyperglycemia, although hyperglycemia was still prevalent in older obese subjects than in older reference-weight subjects. Therefore, the decline in the association may be accelerated due to an age-dependent increase in the prevalence of hyperglycemia in reference-weight individuals.

Healthy eating index and metabolically healthy obesity in U.S. adolescents and adults.

OBJECTIVE: To determine whether dietary quality differs between metabolically-healthy-obese (MHO) and metabolically-abnormal-obesity (MAO) in a nationally representative sample. METHODS: National Health and Nutrition Examination Survey (NHANES) data (2007-2008; 2009-2010) were used to identify obese adolescents (≥95th body mass index (BMI) %tile) and adults (≥30kg/m(2)). MHO was defined as <2 abnormal cardiometabolic risk factors (elevated blood pressure, triglycerides, glucose, low high density lipoprotein cholesterol (HDL-C); or on medications). Healthy Eating Index 2005 (HEI-2005) scores were calculated from 24-hour recall data. General linear regression models determined whether HEI-2005 scores differed between MHO and MAO after controlling for age, race, gender, NHANES wave, BMI, physical activity and health status by age group (12-18; 19-44; 45-85years). RESULTS: Compared with MAO, MHO adolescents (n=133) had higher total HEI-2005 score, higher milk scores, and higher scores from calories from solid fats, alcohol beverages and added sugars. MHO women 19-44years (n=240) had higher total HEI-2005, higher whole fruit, higher whole grain and higher meat and bean scores compared with MAO. No significant differences were observed between MHO and MAO for HEI-2005 total scores in men 19-44years, or adults 45-85years. CONCLUSION: MHO adolescents and women 19-44years have better dietary compliance to the U.S. guidelines when compared with MAO, suggesting potential intervention targets to improve cardiometabolic risk within obesity.

MHO or MUO? White adipose tissue remodeling.

In this review, we delve into the intricate relationship between white adipose tissue (WAT) remodeling and metabolic aspects in obesity, with a specific focus on individuals with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). WAT is a highly heterogeneous, plastic, and dynamically secreting endocrine and immune organ. WAT remodeling plays a crucial role in metabolic health, involving expansion mode, microenvironment, phenotype, and distribution. In individuals with MHO, WAT remodeling is beneficial, reducing ectopic fat deposition and insulin resistance (IR) through mechanisms like increased adipocyte hyperplasia, anti-inflammatory microenvironment, appropriate extracellular matrix (ECM) remodeling, appropriate vascularization, enhanced WAT browning, and subcutaneous adipose tissue (SWAT) deposition. Conversely, for those with MUO, WAT remodeling leads to ectopic fat deposition and IR, causing metabolic dysregulation. This process involves adipocyte hypertrophy, disrupted vascularization, heightened pro-inflammatory microenvironment, enhanced brown adipose tissue (BAT) whitening, and accumulation of visceral adipose tissue (VWAT) deposition. The review underscores the pivotal importance of intervening in WAT remodeling to hinder the transition from MHO to MUO. This insight is valuable for tailoring personalized and effective management strategies for patients with obesity in clinical practice.

Different associations between body mass index and Alzheimer's markers depending on metabolic health.

BACKGROUND: Increasing evidence supports the association between body mass index (BMI), Alzheimer's disease, and vascular markers. Recently, metabolically unhealthy conditions have been reported to affect the expression of these markers. We aimed to investigate the effects of BMI status on Alzheimer's and vascular markers in relation to metabolic health status. METHODS: We recruited 1,736 Asians without dementia (71.6 ± 8.0 years). Participants were categorized into underweight, normal weight, or obese groups based on their BMI. Each group was further divided into metabolically healthy (MH) and unhealthy (MU) groups based on the International Diabetes Foundation definition of metabolic syndrome. The main outcome was Aß positivity, defined as a Centiloid value of 20.0 or above and the presence of vascular markers, defined as severe white matter hyperintensities (WMH). Logistic regression analyses were performed for Aß positivity and severe WMH with BMI status or interaction terms between BMI and metabolic health status as predictors. Mediation analyses were performed with hippocampal volume (HV) and baseline Mini-Mental State Examination (MMSE) scores as the outcomes, and linear mixed models were performed for longitudinal change in MMSE scores. RESULTS: Being underweight increased the risk of Aß positivity (odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.13-4.98), whereas obesity decreased Aß positivity risk (OR = 0.63, 95% CI 0.50-0.80). Especially, obesity decreased the risk of Aß positivity (OR = 0.38, 95% CI 0.26-0.56) in the MH group, but not in the MU group. Obesity increased the risk of severe WMH (OR = 1.69, 1.16-2.47). Decreased Aß positivity mediate the relationship between obesity and higher HV and MMSE scores, particularly in the MH group. Obesity demonstrated a slower decline in MMSE (ß = 1.423, p = 0.037) compared to being normal weight, especially in the MH group. CONCLUSIONS: Our findings provide new evidence that metabolic health has a significant effect on the relationship between obesity and Alzheimer's markers, which, in turn, lead to better clinical outcomes.