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.

Effects of a long-term lifestyle intervention on metabolically healthy women with obesity: Metabolite profiles according to weight loss response.

BACKGROUND & AIMS: The benefits of weight loss in subjects with metabolically healthy obesity (MHO) are still a matter of controversy. We aimed to identify metabolic fingerprints and their associated pathways that discriminate women with MHO with high or low weight loss response after a lifestyle intervention, based on a hypocaloric Mediterranean diet (MedDiet) and physical activity. METHODS: A UPLC-Q-Exactive-MS/MS metabolomics workflow was applied to plasma samples from 27 women with MHO before and after 12 months of a hypocaloric weight loss intervention with a MedDiet and increased physical activity. The subjects were stratified into two age-matched groups according to weight loss: <10% (low weight loss group, LWL) and >10% (high weight loss group, HWL). Random forest analysis was performed to identify metabolites discriminating between the LWL and the HWL as well as within-status effects. Modulated pathways and associations between metabolites and anthropometric and biochemical variables were also investigated. RESULTS: Thirteen metabolites discriminated between the LWL and the HWL, including 1,5-anhydroglucitol, carotenediol, 3-(4-hydroxyphenyl)lactic acid, N-acetylaspartate and several lipid species (steroids, a plasmalogen, sphingomyelins, a bile acid and long-chain acylcarnitines). 1,5-anhydroglucitol, 3-(4-hydroxyphenyl)lactic acid and sphingomyelins were positively associated with weight variables whereas N-acetylaspartate and the plasmalogen correlated negatively with them. Changes in very long-chain acylcarnitines and hydroxyphenyllactic levels were observed in the HWL and positively correlated with fasting glucose, and changes in levels of the plasmalogen negatively correlated with insulin resistance. Additionally, the cholesterol profile was positively associated with changes in acid hydroxyphenyllactic, sphingolipids and 1,5-AG. CONCLUSIONS: Higher weight loss after a hypocaloric MedDiet and increased physical activity for 12 months is associated with changes in the plasma metabolome in women with MHO. These findings are associated with changes in biochemical variables and may suggest an improvement of the cardiometabolic risk profile in those patients that lose greater weight. Further studies are needed to investigate whether the response of those subjects with MHO to this intervention differs from those with unhealthy obesity.

Obesity and the Obesity Paradox in Heart Failure.

Obesity continues to be a public health problem in the general population, and also significantly increases the risk for the development of new-onset heart failure (HF). However, in patients with already-established, chronic HF, overweight and mild to moderate obesity is associated with substantially improved survival compared to normal weight patients; this has been termed the "obesity paradox". The majority of studies measure obesity by body mass index, but studies utilizing less-frequently used measures of body fat and body composition, including waist circumference, waist-hip ratio, skinfold estimates, and bioelectrical impedance analysis also confirm the obesity paradox in HF. Other areas of investigation such as the relationship of the obesity paradox to cardiorespiratory fitness, gender, and race are also discussed. Finally, this review explores various explanations for the obesity paradox, and summarizes the current evidence for intentional weight loss treatments for HF in context.

"Metabolically Healthy" Obesity: Fact or Threat?

INTRODUCTION: Obesity is a serious, worldwide and growing problem, with associated complications ranging from cardiovascular disease to cancer. It has been suggested that a subgroup of obese patients- the "metabolically healthy" (MH)- would constitute a phenotype whose cardiovascular risk would be closer to that of normal weight individuals and lower than that of obese patients with other risk factors. The definitions of MH obesity are heterogeneous, what makes the estimation of its prevalence quite difficult. Besides that, data are still controversial about the risk of incident cardiovascular disease in these patients and therefore this remains an unresolved matter. In parallel, the possibly lower risk of MH obesity may raise questions about the need for weight loss in MH obese patients. CONCLUSION: This issue should be carefully addressed, and evidence for a "benign" profile of MH obesity critically evaluated, as obesity is a risk factor for numerous health outcomes, and weight loss in obese people additionally offers protection against these nonmetabolic diseases.