Metabolically Obese Normal-weight Phenotype Research Articles

The Metabolically Obese, Normal-Weight Phenotype in Young Rats Is Associated with Cognitive Impairment and Partially Preventable with Leptin Intake during Lactation.

The intake of high-fat diets (HFDs) and obesity are linked to cognitive impairment. Here, we aimed to investigate whether an early metabolically obese, normal-weight (MONW) phenotype, induced with an HFD in young rats, also leads to cognitive dysfunction and to evaluate the potential cognitive benefits of neonatal intake of leptin. To achieve this, Wistar rats orally received physiological doses of leptin or its vehicle during lactation, followed by 11 weeks of pair-feeding with an HFD or control diet post-weaning. Working memory was assessed using a T-maze, and gene expression in the hippocampus and peripheral blood mononuclear cells (PBMCs) was assessed with real-time RT-qPCR to identify cognition biomarkers. Young MONW-like rats showed hippocampal gene expression changes and decreased working memory. Animals receiving leptin during lactation presented similar gene expression changes but preserved working memory despite HFD intake, partly due to improved insulin sensitivity. Notably, PBMC Syn1 expression appears as an accessible biomarker of cognitive health, reflecting both the detrimental effect of HFD intake at early ages despite the absence of obesity and the positive effects of neonatal leptin treatment on cognition. Thus, the MONW phenotype developed at a young age is linked to cognitive dysfunction, which is reflected at the transcriptomic level in PBMCs. Neonatal leptin intake can partly counteract this impaired cognition resulting from early HFD consumption.

Metabolically Obese Normal-Weight Phenotype as a Risk Factor for High Blood Pressure: A Five-Year Cohort

Background: The metabolically obese normal-weight (MONW) phenotype has been considered a risk factor for different chronic diseases, but its role in high blood pressure (HBP) is still unclear. The aim of the study is to determine if the MONW phenotype constitutes a risk factor for hypertension in Peruvian adults belonging to a 5-year cohort. Methods: This is a retrospective cohort study. A secondary analysis from the database of the PERU MIGRANT study was carried out from the MONW and non-MONW cohorts; after a 5-year follow-up, the appearance of HBP was evaluated in the subjects of both cohorts. To assess the strength and magnitude of the association, a Poisson regression model (crude and adjusted) with robust variance was used. The measure of association was the relative risk (RR). Results: The incidence of HBP was 11.30%. In the multivariable analysis, subjects with the MONW phenotype had a 2.879-fold risk of presenting HBP in 5 years compared with those who were not MONW at the beginning of the study; this was adjusted for categorized age, sex, group, and state of smoker and alcohol drinker (RR: 2.055; 95% confidence interval (CI): 1.118 - 3.777; P = 0.020). Conclusions: The presence of the MONW phenotype doubled the incidence of HBP, even after adjusting for other covariates. However, studies in this field should continue. If these findings are confirmed, it should be considered that presenting an adequate weight for height should not be interpreted as a condition free of metabolic alterations, so screening for hypertension should be carried out regardless of whether or not the body mass index obtained is considered normal. J Endocrinol Metab. 2023;13(1):13-19 doi: https://doi.org/10.14740/jem855

Hyperuricemia is Associated with the Presence of Metabolically Obese Normal-Weight and Metabolically Healthy Obese Phenotypes

ABSTRACT Background It is well-recognized that hyperuricemia is a common abnormality among individuals with metabolic syndrome. Aims The objective of this study was to determine whether hyperuricemia is associated with the metabolically obese normal-weight (MONW) and metabolically healthy obese (MHO) phenotypes. Methods Men and women equal or greater than 18 years of age were enrolled in a cross-sectional study. Normal-weight subjects were allocated into the MONW or healthy normal-weight (HNW) groups; while obese individuals were divided into the MHO and metabolically unhealthy obese (MUO) subgroups. MONW phenotype was defined by body mass index (BMI) <25.0 kg/m2 accompanied by at least one cardiovascular risk factor (hyperglycemia, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol), and MHO phenotype was considered in obese subjects (BMI ≥30 kg/m2) without metabolic abnormalities. Results A total of 567 individuals were enrolled; of them, normal-weight subjects were allocated into the MONW (n = 101) and control (n = 72) groups, whereas obese individuals into the MHO (n = 61) and MUO (n = 333) groups. The multiple logistic regression analysis adjusted by age, gender, and body mass index revealed that hyperuricemia is significantly associated with MONW (OR = 5.14; 95% CI: 1.37–19.29) and MHO (OR = 0.34; 95% CI: 0.14–0.82) phenotypes. Conclusion Results of our study showed that hyperuricemia is associated with both MONW and MHO phenotypes.

Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats

Perinatal nutrition has a well-known influence on obesity susceptibility. We previously demonstrated the protective anti-obesity effects of perinatal leptin administration. Celastrol is a natural compound acting as a leptin sensitizer with anti-obesity effects when administered in adult animals. Here, we aimed to determine if perinatal treatment with leptin, celastrol, or their combination was able to improve metabolic health in animals fed an isocaloric high-fat (HF) diet. Leptin and/or celastrol or their vehicle were administered orally to rats during the suckling period. After weaning, animals were chronically pair-fed with an HF diet provided isocaloric to the intake of a normal-fat diet by control animals to avoid obesity. Isocaloric HF feeding in vehicle-treated animals resulted in metabolic features characteristic of the metabolically obese, normal-weight (MONW) phenotype, i.e., obesity-related disturbances without increased body weight. Leptin treatment prevented liver fat deposition and insulin resistance, induced greater insulin and leptin signaling capacity, decreased gene expression of orexigenic signals at the hypothalamic level, and induced browning in retroperitoneal adipose tissue. However, celastrol treatment did not provide any protective effect and resulted in greater size of the retroperitoneal adipose depot, higher circulating glucose and insulin levels, and decreased leptin sensitivity capacity in adipose tissue. The co-administration of leptin ameliorated the negative effects of celastrol on the retroperitoneal depot, inducing browning and decreasing its size. In conclusion, the perinatal administration of leptin, but not celastrol, provided protection against the consequences of dietary unbalances leading to an MONW phenotype in adulthood.

Sex Differences in the TyG Index and Cardiovascular Risk Factors in Metabolically Obese Normal Weight Phenotype.

Background The triglyceride glucose (TyG) index is a novel surrogate marker of insulin resistance and increases cardiovascular disease risk. We sought to explore sex differences in the relationship between TyG and cardiovascular (CV) risk factors in metabolically obese normal weight (MONW) phenotype. Method We analyzed data of 1208 healthy men and nonpregnant women enrolled in a population-based longitudinal study from January 2017–June 2020. MONW phenotype was defined by normal body mass index (BMI: 18–<25 kg/m2) with at least one of the following metabolic disorders (MONW phenotype): elevated blood pressure (BP), hypertriglyceridemia, hyperglycemia, and low HDL cholesterol. Multiple logistic regression analysis was performed to assess the association between elevated TyG index and the CV risk factors in women and men and was presented in odds ratio (OR) with 95% confidence interval (CI). Results Of 1208 subjects, 350 (29%) were MONW phenotype (mean age (years): male: 43.5 ± 12.4 and female: 43.1 ± 12.7) and 858 were metabolically healthy normal weight (MHNW; n = 858 (71%)). MONW women had higher mean values of the TyG index (8.03 ± 5.07) than men (7.47 ± 4.68). Multivariate analysis revealed that the elevated TyG index is significantly associated with MONW phenotype in women (adjusted OR: 8.73, 95% CI: 5.62–13.57) and men (aOR: 5.90, 95% CI: 4.23–8.23). TyG was found to be an excellent predictor of MONW status in both women (receiver operating characteristic (ROC) area under the curve (AUC): 0.979, 95% CI: 0.969–0.988) and men (ROC-AUC: 0.968, 95% CI: 0.952–0.983). Conclusion Our study revealed that the TyG index may represent a cost-effective and informative screening tool for the high-risk MONW phenotype.

Anthropometric and body composition parameters in adolescents with the metabolically obese normal-weight phenotype.

We aimed to investigate the anthropometric and body composition parameters associated with the metabolically obese normal-weight (MONW) phenotype. This cross-sectional study was conducted with 506 adolescents in Brazil (aged 10-19 y). The MONW phenotype was defined as normal-weight, according to BMI/age, and at least one metabolic alteration. Anthropometric measurements were obtained and the DEXA was used for body composition analysis. Crude and adjusted Poisson regression models with robust variance were used to estimate the associations. The phenotype was positively associated with waist circumference (male: prevalence ratio (PR) = 1·05; 95% CI 1·01, 1·09; female: PR = 1·06; 95% CI 1·02, 1·09), waist:height ratio (male: PR = 1·26; 95% CI 1·07, 1·49; female: PR = 1·29; 95% CI 1·07, 1·56) and android:gynoid fat ratio (male: PR = 1·25; 95% CI 1·03, 1·51; female: PR = 1·39; 95% CI 1·20, 1·62), in both sexes. Furthermore, there was a positive association of phenotype with waist:hip ratio (PR = 1·32; 95% CI 1·06, 1·65) and trunk:arm fat ratio (PR = 1·13; 95% CI 1·02, 1·24) only in males and with trunk:leg fat ratio (PR = 2·84; 95% CI 1·46, 5·53), BAIp (PR = 1·06; 95% CI 1·01, 1·12), fat mass index (PR = 1·24; 95% CI 1·10, 1·41) and regional indices of metabolic load and capacity (PR = 1·29; 95% CI 1·09, 1·53), in females. Anthropometric and body composition parameters indicative of central and total fat are associated with the MONW phenotype.

Prevalence and characteristics of the metabolically healthy obese phenotype in children and adolescents in a Mexican state

ObjectivesTo determine the prevalence of the Metabolically Healthy Obesity (MHO), and Metabolically Obese Normal-Weight (MONW) phenotypes in a sample of children and adolescents. To evaluate which clinical and laboratory variables are related to the MONW and MHO phenotypes. MethodsA cross-sectional study was carried out in children and adolescents aged 6-18 years old, presumably healthy. Somatometry, glucose, insulin, triglycerides, HDL-cholesterol, LDL-cholesterol, HOMA-IR, triglycerides/HDL ratio, triglycerides and glucose index, and leptin/adiponectin, were determined. ResultsData from 620 children and adolescents were included (50.65% were males); the median age was 11 years. The prevalence of the MONW phenotype was 22.85% (95%CI 16.85%-29.79%), and the MHO phenotype 27.61% (95%CI 22.60%-33.06%). The variables that significantly explained the possibility of presenting the MONW and MHO phenotype were triglycerides/HDL ratio, and product of triglycerides and glucose. Insulin and HOMA-IR were significantly associated with the MHO phenotype but not with the MONW phenotype. ConclusionsPrevalence of metabolically healthy obese phenotype is lower in the Mexican population compared to European studies; thus, future studies should determine if this difference relies upon genetic profile or lifestyle. The indices to assess the action of insulin based on lipids can help identify children and adolescents with the MHO and MONW phenotypes.

Prevalence and characteristics of the metabolically healthy obese phenotype in children and adolescents in a Mexican state

ObjectivesTo determine the prevalence of the Metabolically Healthy Obesity (MHO), and Metabolically Obese Normal-Weight (MONW) phenotypes in a sample of children and adolescents. To evaluate which clinical and laboratory variables are related to the MONW and MHO phenotypes. MethodsA cross-sectional study was carried out in children and adolescents aged 6-18 years old, presumably healthy. Somatometry, glucose, insulin, triglycerides, HDL-cholesterol, LDL-cholesterol, HOMA-IR, triglycerides/HDL ratio, triglycerides and glucose index, and leptin/adiponectin, were determined. ResultsData from 620 children and adolescents were included (50.65% were males); the median age was 11 years. The prevalence of the MONW phenotype was 22.85% (95%CI 16.85%-29.79%), and the MHO phenotype 27.61% (95%CI 22.60%-33.06%). The variables that significantly explained the possibility of presenting the MONW and MHO phenotype were triglycerides/HDL ratio, and product of triglycerides and glucose. Insulin and HOMA-IR were significantly associated with the MHO phenotype but not with the MONW phenotype. ConclusionsPrevalence of metabolically healthy obese phenotype is lower in the Mexican population compared to European studies; thus, future studies should determine if this difference relies upon genetic profile or lifestyle. The indices to assess the action of insulin based on lipids can help identify children and adolescents with the MHO and MONW phenotypes.

Cardiometabolic index: a new tool for screening the metabolically obese normal weight phenotype.

People with the metabolically obese normal weight (MONW) phenotype are considered as an extremely high-risk group for unfavorable health consequences, but they are frequently undetected due to deceptive body mass index (BMI) and complex assessment. This study aimed to explore the clinical usefulness of cardiometabolic index (CMI) in identifying MONW individuals. This cross-sectional study involved a total of 47,683 normal-weight subjects aged ≥ 18years. Participants underwent anthropometrics, routine biochemical tests, and questionnaires for a full evaluation of the metabolic profile. The odds ratio (OR) of CMI and MONW phenotype was determined by the Logistic regression models and the diagnostic accuracy of CMI was evaluated by the receiver operating characteristic (ROC) curve analysis. The prevalence of MONW phenotype was 11.0%. After multivariate adjustment, the ORs for MONW in the highest compared with the lowest quartile of CMI was 71.20 (95% CI 55.19-91.86), and 1-SD increment of CMI brought a 54% additional risk. In ROC analysis, compared with BMI and waist circumference, CMI showed superior performance for identifying MONW individuals with an AUC of 0.853 (95% CI 0.847-0.860) in men and 0.912 (95% CI 0.906-0.918) in women, respectively. Moreover, CMI exhibited the highest diagnostic accuracy in younger age groups (aged 18-34 for men; aged 18-34 and 35-44 for women), in which AUCs surpassed 0.9 in both sexes. CMI could be served as a valuable indicator to identify MONW phenotype of Chinese adults, particularly for young people.

Interaction between early environment and genetic predisposition instigates the metabolically obese, normal weight phenotype in children: findings from the BCAMS study.

A subset of normal-weight individuals appears predisposed to obesity-related cardiometabolic abnormalities. Studies of this metabolically obese, normal weight (MONW) phenotype in youth are scarce. We aimed to identify early environmental and genetic factors associated with MONW in children. Overall, 1475 normal-weight Chinese children aged 6-18 were recruited from the Beijing Children and Adolescents Metabolic Syndrome study cohort. Birthweight, childhood lifestyle, socio-economic factors, and 20 genetic variants previously shown to be associated with BMI or glucose metabolism in East Asian adults were examined for their association with the MONW phenotype. MONW was defined by exhibiting any metabolic syndrome component. After adjusting for covariates including BMI, low birthweight and low levels of physical activity, fruit consumption, parental education and household income, as well as CDKAL1 rs2206734 genotype were independent predictors of the MONW phenotype (all P < 0.05). Moreover, rs2206734 interacted with birthweight to predict the MONW phenotype (Pinteraction = 0.0008). Among high (>75th percentile) birthweight individuals, each C allele at this locus was associated with a 62% reduced risk of MONW (OR = 0.38; 95% CI = 0.26-0.58; P = 5.71 × 10-6), while no such genetic associations were found in intermediate or low birthweight individuals (P > 0.1). This CDKAL1-MONW relationship in high birthweight individuals was especially strong in the presence of favorable childhood environmental factors (high levels of physical activity, fruit consumption, parental education and household income) (Pinteraction = 0.013). Our findings provided the novel evidence that early environment (especially birthweight) and genetics, along with their interaction with one another, play important roles in predicting the MONW phenotype among children.

The triglycerides and glucose index is associated with cardiovascular risk factors in metabolically obese normal-weight subjects.

The aim of this study was to determine whether the triglycerides and glucose (TyG) index is associated with the presence of metabolically obese normal-weight (MONW) phenotype and related cardiovascular risk factors. Apparently healthy men and non-pregnant women aged 20-65years were enrolled in a population-based cross-sectional study. Overweight, obesity, smoking, alcohol consumption, pregnancy, diagnosis of hypertension, diabetes, cardiovascular disease, liver disease, renal disease, malignancy, and medical treatment were exclusion criteria. Subjects were allocated into the MONW or normal-weight groups. MONW phenotype was defined by normal weight and the presence of at least one of the following cardiovascular risk factors: elevated blood pressure, hyperglycemia, hypertriglyceridemia, and low HDL cholesterol. A total of 542 subjects were enrolled and allocated into the MONW (n = 354) and normal-weight (n = 188) groups. The adjusted logistic regression analysis showed that the elevated TyG index is significantly associated with the presence of MONW phenotype (OR = 11.14; 95% CI 6.04-20.57), hyperglycemia (OR = 3.18; 95% CI 1.95-5.21), hypertriglyceridemia (OR = 399.19; 95% CI 94.01-1694.98), and low HDL-C (OR = 2.60; 95% CI 1.74-3.87), but not with elevated blood pressure (OR = 1.55; 95% CI 0.93-2.60). Results of this study support that the TyG index may be a useful indicator to detect MONW phenotype and associated cardiovascular risk factors.

1322-P: Early Environment and Genetic Predisposition to Metabolically Obese Normal-Weight Phenotype in Children: Findings from a Cohort Study

Some normal-weight individuals are predisposed to obesity-related cardiometabolic abnormalities, namely, metabolically obese normal weight (MONW). Studies of the MONW phenotype in youths are scarce. We aimed to identify early environmental and genetic factors associated with MONW in children. Overall, 1,484 normal-weight Chinese children aged 6-18, including 588 subjects with MONW phenotype, were recruited from the Beijing Children and Adolescents Metabolic Syndrome cohort. Birth weight (BW) childhood lifestyle and socio-economic factors, and 20 genetic variants which had been previously shown to be associated with BMI or T2D in East Asian adults were examined for the associations with pediatric MONW phenotype. Metabolically unhealthy was defined as having any metabolic syndrome component or HOMA-IR≥3.0. Independent risk factors for MONW phenotype were low BW, increased BMI, and lower levels of physical activity, maternal education and family income (all P&amp;lt;0.05), while amongst genetic variants, CDKAL1 rs2206734 shown the strongest association with MONW (OR per C allele=0.81, 95% CI=0.70-0.95; P=0.008). Moreover, rs2206734 interacted with BW on MONW phenotype (P interaction=0.005). Every C allele was associated with a 50% reduced risk of MONW in high (&amp;gt;75th percentile) BW (95% CI=0.34-0.72; P=0.0002), while the genetic associations were nonsignificant in intermediate and low (≤75th percentile) BW (P&amp;gt;0.1). The effect of high BW on the CDKAL1-MONW relationship could be further augmented by the combined impact of beneficial childhood environmental factors (physically active, high maternal education and family income) (Pinteraction=0.017). In conclusion, both early environments, particularly BW, and genetic predisposition plus their interaction were associated with MONW in children. Our study provides new insights into MONW and suggests a long-term prevention strategy, especially in genetically susceptible individuals. Disclosure M. Li: None. G. Li: None. S. Gao: None. S.M. Willi: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Roche Diagnostic USA. Research Support; Self; Jaeb Center for Health Research, National Institute of Allergy and Infectious Diseases, Sanofi-Aventis. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Funding National Key Research Program of China (2016YFC1304801); Beijing Municipal Science &amp; Technology Commission (D111100000611001, D111100000611002); Beijing Natural Science Foundation (7172169); Beijing Science &amp; Technology Star Program (2004A027), Novo Nordisk (2011A002); National Key Program of Clinical Science (WBYZ 2011-873); Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT32020, 2018PT32001)

Regulation of glucose metabolism in nondiabetic, metabolically obese normal-weight Asians

Type 2 diabetes in Asia occurs largely in the absence of obesity. The metabolically obese normal-weight (MONW) phenotype refers to lean subjects with metabolic dysfunction that is typically observed in people with obesity and is associated with increased risk for diabetes. Previous studies evaluated MONW subjects who had greater body mass index (BMI) or total body fat than respective control groups, making interpretation of the results difficult. We evaluated insulin sensitivity (hyperinsulinemic-euglycemic clamp); insulin secretion (mixed meal with oral minimal modeling); intra-abdominal, muscle, and liver fat contents (magnetic resonance); and fasting and postprandial glucose and insulin concentrations in 18 MONW subjects and 18 metabolically healthy controls matched for age (43 ± 3 and 40 ± 3 yr; P = 0.52), BMI (both 22 ± 1 kg/m2; P = 0.69), total body fat (17 ± 1 and 16 ± 1 kg; P = 0.33), and sex (9 men and 9 women in each group). Compared with controls, MONW subjects had an approximately twofold greater visceral adipose tissue volume and an approximately fourfold greater intrahepatic fat content (but similar muscle fat), 20-30% lower glucose disposal rates and insulin sensitivity, and 30-40% greater insulin secretion rates (all P < 0.05). The disposition index, fasting glucose, and HbA1c concentrations were not different between groups, whereas postprandial glucose and insulin concentrations were ~15% and ~65% greater, respectively, in MONW than control subjects (both P < 0.05). We conclude that the MONW phenotype is associated with accumulation of fat in the intra-abdominal area and the liver, profound insulin resistance, but also a robust β-cell insulin secretion response that compensates for insulin resistance and helps maintain glucose homeostasis.

Lean, but not healthy: the 'metabolically obese, normal-weight' phenotype.

Obesity is commonly associated with metabolic dysfunction but there are obese persons who are metabolically healthy. On the opposite side of the coin, there are lean persons who carry multiple cardiometabolic risk factors, typically referred to as metabolically obese, normal-weight (MONW). This has called into question our understanding of obesity and metabolic dysfunction, as an appearance of normal weight may mask significant comorbidities and delay health interventions. High heterogeneity in MONW prevalence rates has been observed, with estimates ranging from as low as 5% to as high as 45%. Reasons for this include sample size effects, differences in MONW definition, social and demographic factors, as well as assumptions made in establishing normal weight. MONW study participants are often characterized by excess visceral adipose tissue and ectopic fat deposition, adipose tissue inflammation, altered inflammatory and adipokine profiles, reduced skeletal muscle mass and low cardiorespiratory fitness. However, more often than not, groups of MONW study participants have been somewhat 'fatter' than the control groups of metabolically healthy lean study participants, which in itself could be responsible for some of the observed differences. Very limited data are available regarding interventions to improve metabolic function in MONW study participants. There is a need for more research to better understand the characteristics of the MONW phenotype, the cause of metabolic dysfunction in the absence of obesity, and evaluate potential therapies so as to facilitate the establishment of clinical guidelines.

Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH) style diet, and metabolic health in U.S. adults

There is sparse evidence on the relationship between the Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH) style diet, and metabolic health, especially comparing cardiometabolic phenotypes among in normal weight and obese populations. We aimed to investigate the association of the Mediterranean diet scores (MDS) and DASH index with metabolically healthy obese (MHO) and metabolically obese normal weight (MONW) phenotypes in a representative U.S. MDS and DASH index were calculated using dietary data from 2767 adults aged 20-90 years without any prior diagnosis of cancer or cardiovascular disease from the National Health and Nutrition Examination Survey III, 1988-1994. MHO and MONW individuals were identified using fasting glucose, insulin resistance, blood pressure, triglycerides, C-reactive protein, and high-density lipoprotein-cholesterol. Higher MDS was associated with higher odds of MHO phenotype (odds ratio (OR)T3 vs T1, 2.57 [95% confidence interval (CI), 1.04-6.35]; P trend=0.04), and higher DASH index was associated with lower odds of MONW phenotype (ORT3 vs T1, 0.59 [95% CI, 0.38-0.93]; P trend=0.03) only in the younger age group (<45 years for men or premenopausal women). No significant associations of MDS and DASH index with MHO and MONW phenotypes were observed in the older age group (≥45 years for men or postmenopausal women). Adherence to Mediterranean diet or DASH style diet was favorably associated with MHO and MONW phenotypes only in the younger age group, suggesting that potential dietary intervention to prevent cardiometabolic disease differ by age group.

Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker of diet-related metabolic alterations

BackgroundResearch on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC) is a promising tool to identify subjects at risk of developing diet-related diseases.ObjectiveWe analysed PBMC expression of key energy homeostasis-related genes in a time-course analysis in order to find out early markers of metabolic alterations due to sustained intake of high-fat (HF) and high-protein (HP) diets.DesignWe administered HF and HP diets (4 months) to adult Wistar rats in isocaloric conditions to a control diet, mainly to avoid overweight associated with the intake of hyperlipidic diets and, thus, to be able to characterise markers of metabolically obese normal-weight (MONW) syndrome. PBMC samples were collected at different time points of dietary treatment and expression of relevant energy homeostatic genes analysed by real-time reverse transcription-polymerase chain reaction. Serum parameters related with metabolic syndrome, as well as fat deposition in liver, were also analysed.ResultsThe most outstanding results were those obtained for the expression of the lipolytic gene carnitine palmitoyltransferase 1a (Cpt1a). Cpt1a expression in PBMC increased after only 1 month of exposure to both unbalanced diets, and this increased expression was maintained thereafter. Interestingly, in the case of the HF diet, Cpt1a expression was altered even in the absence of increased body weight but correlated with alterations such as higher insulin resistance, alteration of serum lipid profile and, particularly, increased fat deposition in liver, a feature characteristic of metabolic syndrome, which was even observed in animals fed with HP diet.ConclusionsWe propose Cpt1a gene expression analysis in PBMC as an early biomarker of metabolic alterations associated with MONW phenotype due to the intake of isocaloric HF diets, as well as a marker of increased risk of metabolic diseases associated with the intake of HF or HP diets.

Lipid accumulation product and visceral adiposity index are effective markers for identifying the metabolically obese normal-weight phenotype.

Studies have identified the metabolically obese normal-weight (MONW) phenotype, which carries increased risk of diabetes and cardiovascular disease. We aimed to investigate the ability of lipid accumulation product (LAP) and visceral adiposity index (VAI), two markers of visceral obesity, to identify the MONW phenotype. Normal-weight participants [body mass index (BMI) being of 18.5-23 kg/m(2)] (n = 3,552; 46.9 % men) in the 2009 nationwide China Health and Nutrition Survey were included in our analysis. Four different criteria that have been published were used to define the MONW phenotype. LAP and VAI were calculated according to published formula. Receiver operating characteristic (ROC) curve analysis revealed that, regardless of the definition used to define MONW phenotype, both LAP [area under the ROC curve (AUC) ranging from 0.606 to 0.807 depending on the criteria used for MONW phenotype] and VAI (AUC ranging from 0.611 to 0.835 depending on the criteria used for MONW phenotype) outperformed anthropometric parameters including BMI, waist circumference, waist-to-hip ratio, and waist-to-height ratio for identifying MONW phenotype. Both LAP and VAI were strongly related to the MONW phenotype, irrespective of the criteria used to define the MONW phenotype. The associations between the 4th quartile of LAP and the MONW phenotype or between the 4th quartile of VAI and the MONW phenotype were consistently seen in various subgroups. Our study demonstrates that both LAP and VAI are effective markers for identifying the Chinese adults with MONW phenotype.

Oral Magnesium Supplementation Improves the Metabolic Profile of Metabolically Obese, Normal-weight Individuals: A Randomized Double-blind Placebo-controlled Trial

We undertook this study to determine the efficacy of oral magnesium supplementation in the improvement of the metabolic profile and blood pressure in metabolically obese, normal-weight (MONW) individuals. A total of 47 MONW individuals with hypomagnesemia were enrolled in clinical a randomized double-blind placebo-controlled trial. Individuals in the intervention group received 30 mL of MgCl2 5% solution (equivalent to 382 mg of magnesium) and individuals in the control group 30 mL of placebo solution, once daily during 4 months. In the absence of obesity or overweight, the presence of fasting glucose levels ≥100 mg/dL, HOMA-IR index ≥3, triglyceride levels ≥150 mg/dL and/or systolic and diastolic blood pressure ≥140 and 90 mmHg defined the presence of the MONW phenotype. Hypomagnesemia was defined by serum magnesium concentration ≤1.8 mg/dL. At basal conditions there were no significant differences between groups. At the end of follow-up, changes in the mean of systolic (-2.1 vs. 3.9% mmHg, p <0.05) and diastolic (-3.8 vs. 7.5% mmHg, p <0.05) blood pressures, HOMA-IR index (-46.5 vs. -5.4%, p <0.0001), fasting glucose (-12.3 vs. -1.8% mg/dL, p <0.05) and triglyceride levels (-47.4% vs. 10.1% mg/dL, p <0.0001) were significantly lower in the subjects who received MgCl2 compared with individuals in the control group. Oral magnesium supplementation improves the metabolic profile and blood pressure of MONW individuals.

Higher mortality in metabolically obese normal‐weight people than in metabolically healthy obese subjects in elderly Koreans

The purpose of this study was to investigate the impact of body mass index (BMI) and the presence of metabolic syndrome (MetS) on all-cause and cardiovascular mortality in elderly Korean men and women, and especially to compare metabolically obese normal-weight (MONW) and metabolically healthy obese (MHO) subjects. A total of 2317 elderly people (over 60 years of age) were studied using follow-up data from the South-West Seoul (SWS) Study, a prospective cohort study. Mortality from all causes and cardiovascular disease (CVD) were evaluated according to the combination of the presence or absence of MetS and Asian-specific body mass index (BMI) criteria (BMI <23 kg/m²; normal weight, BMI 23-24·9 kg/m²; overweight, BMI ≥25 kg/m²; obesity). During a median follow-up of 10·3 years, 393 subjects died, including 126 from CVD. Among subjects with MetS, all-cause and CVD mortality were significantly higher in normal-weight subjects than overweight or obese individuals in Cox proportional-hazard models adjusted for confounding factors. Furthermore, among six groups with various MetS/BMI combinations, MONW individuals had the highest risk, whereas overweight subjects without MetS had the lowest risk of death from all causes and CVD [HR = 2·2 (95% CI = 1·4-3·4), HR = 3·0 (95% CI = 1·4-6·6) respectively]. Interestingly, all-cause mortality was significantly higher in MONW than MHO individuals. In contrast to MHO subjects, elderly individuals with the MONW phenotype exhibited greater all-cause mortality during 10 years of follow-up.

Serum magnesium in the metabolically-obese normal-weight and healthy-obese subjects

BackgroundGiven that hypomagnesemia is related with hyperglycemia, hypertension, hypertriglyceridemia, and insulin resistance, the objective of this study was to determine whether serum magnesium levels are associated with the metabolically obese normal weight (MONW) and the metabolically healthy obese (MHO) phenotypes. MethodsPopulation-based cross-sectional study that enrolled 427 subjects, men and non-pregnant women aged 20 to 65years, to participate in the study. Subjects were allocated into groups with and without obesity; among non-obese individuals, the subgroup of MONW subjects was compared with a control group of healthy normal-weight individuals. Among obese individuals, the subgroup of MHO subjects was compared with a control group of obese subjects who exhibited at least one metabolic abnormality. In the absence of obesity, the presence of fasting hyperglycemia, insulin resistance, hypertriglyceridemia, and/or hypertension defined the presence of MONW phenotype. In the absence of hypertension, insulin resistance and metabolic abnormalities of fasting glucose and triglycerides levels, the phenotypically obese subjects were defined as MHO individuals. ResultsThe sex-adjusted prevalence of MONW and MHO phenotypes was 40.8% and 27.9%. The multivariate logistic regression model adjusted by family history of diabetes, age, body mass index, and waist-circumference, showed a positive association between hypomagnesemia and the MONW phenotype (OR 6.4; 95%CI 2.3–20.4) and negative relationship between serum magnesium and the MHO phenotype (OR 0.32; 95%CI 0.17–0.61). ConclusionsOur results show that hypomagnesemia is positively associated with the presence of MONW phenotype, and the normomagnesemia negatively with the MHO phenotype.