Identification of biomarkers related to metabolically unhealthy obesity in Korean obese adolescents: A cross-sectional study

BackgroundObesity is classified as metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO). The current study aimed to screen for relationships and different potential metabolic biomarkers involved between MHO and MUO in adolescents.MethodsThe study included 148 obese adolescents aged between 14 and 16. The study participants were divided into MUO and MHO groups based on the age-specific adolescent metabolic syndrome (MetS) criteria of the International Diabetes Federation. The current study was conducted to investigate the clinical and metabolic differences (AbsoluteIDQ™ p180 kit) between adolescents in the MHO group and those in the MUO group. Multivariate analyses were conducted to investigate the metabolites as independent predictors for the odds ratio and the presence of the MetS in adolescents.ResultsThere were significant differences in the 3 acylcarnitines, 5 amino acids, glutamine/glutamate ratio, 3 biogenic amines, and 2 glycerophospholipids between the obese adolescents in the MUO group and those in the MHO group. Moreover, several metabolites were associated with the prevalence of MUO in adolescents. Additionally, several metabolites were inversely correlated with MHO in adolescents of the MUO group.ConclusionsWe observed that histidine, lysine, PCaaC34:1, and several clinical factors in adolescents of the MUO group were reverse correlated with the results in adolescents of the MHO group. In addition, the triglyceride-glucose index was related to MUO in adolescents, compared with the homeostasis model assessment of insulin resistance. Thus, the biomarkers found in this study have a potential to reflect the clinical outcomes of MUO in adolescents. These biomarkers will lead to a better understanding of MetS in obese adolescents.

Association of Metabolically Healthy and Unhealthy Obesity Phenotype with Markers Related to Obesity, Diabetes among Young, Healthy Adult Men. Analysis of MAGNETIC Study

Adipose tissue secretes many regulatory factors called adipokines. Adipokines affect the metabolism of lipids and carbohydrates. They also influence the regulation of the immune system and inflammation. The current study aimed to evaluate the association between markers related to obesity, diabesity and adipokines and metabolically healthy and unhealthy obesity in young men. The study included 98 healthy participants. We divided participants into three subgroups based on body mass index and metabolic health definition: 49 metabolically healthy normal-weight patients, 27 metabolically healthy obese patients and 22 metabolically unhealthy obese patients. The 14 metabolic markers selected were measured in serum or plasma. The analysis showed associations between markers related to obesity, diabesity and adipokines in metabolically healthy and unhealthy obese participants. The decreased level of adipsin (p < 0.05) was only associated with metabolically healthy obesity, not with metabolically unhealthy obesity. The decreased level of ghrelin (p < 0.001) and increased level of plasminogen activator inhibitor-1 (p < 0.01) were only associated with metabolically unhealthy obesity, not with metabolically healthy obesity. The decreased level of adiponectin and increased levels of leptin, c-peptide, insulin and angiopoietin-like 3 protein were associated with metabolically healthy and unhealthy obesity. In conclusion, our data show that metabolically healthy obesity was more similar to metabolically unhealthy obesity in terms of the analyzed markers related to obesity and diabesity.

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.

Biochemical predictors of metabolically unhealthy obesity in children and adolescents

Background Children and adolescents with obesity can now be classified according to metabolic profile, as those with metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUO). We aimed to determine the prevalence of MUO and identify its biochemical predictors in pediatric patients with obesity. Methods We evaluated the medical records of 187 boys and girls with obesity. The children were divided into MHO and MUO groups, and anthropometric and biochemical parameters were assessed. Oral glucose tolerance test (OGTT) was used to identify impaired glucose regulation and hyperinsulinism, and binary logistic regression analysis was used to determine predictors of MUO in children with obesity. Results Of the 187 children, MUO was found in 71.7% (n=134) and MHO in 28.3% (n=53); those in the MHO group were younger than those in the MUO group. Blood pressure, triglyceride, total cholesterol, and uric acid levels were significantly higher in the MUO group than in the MHO group. Further, the MUO group exhibited a significantly higher level of insulin resistance (p<0.05) than the MHO group. Serum levels of uric acid and homeostasis model assessment of insulin resistance index (HOMA-IR) were confirmed as biochemical predictors of the MUO phenotype in children with obesity. Conclusions The ratio of MUO in children with obesity was relatively high; further, serum levels of uric acid and HOMA-IR can be used as biochemical predictors of MUO.

Do Temporal Eating Patterns Differ in Healthy Versus Unhealthy Overweight/Obese Individuals?

This study examined whether the temporal patterns of energy and macronutrient intake in early and late eating windows were associated with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) among non-shift workers. A total of 299 overweight/obese non-shift workers (Age: 40.3 ± 6.9 years; 73.6% women; BMI: 31.7 ± 5.0 kg/m2) were recruited in the Klang Valley area of Malaysia. The biochemical parameters were determined from fasting blood samples, whereas information on dietary intake and timing was obtained from a 7-day diet history questionnaire. The midpoint of eating was used to determine the early and late windows. Compared to MHO non-shift workers (n = 173), MUO non-shift workers (n = 126) had lower energy intake from carbohydrates and protein during the early window. In contrast, MUO participants had greater energy intake from carbohydrates and fat during the late window. Participants with unhealthy metabolic status (regardless of their chronotypes) had similar temporal patterns of energy intake characterized by smaller energy intake during the early window and greater energy intake during the late window compared with participants with healthier metabolic status. Overall, the lowest percentile of energy intake during the early window was associated with an increased risk of MUO, after adjustment for potential confounders [odds ratio (OR) = 4.30, 95% confidence interval (CI) 1.41–13.11]. The greater the energy intake during the late window, the greater the risk of MUO (OR = 2.38, 95% CI 1.11–5.13) (OR = 2.33, 95% CI 1.03–5.32) (OR = 4.45, 95% CI 1.71–11.56). In summary, consuming less energy earlier in the day and more energy and carbohydrate later in the day was associated with a greater risk of MUO. Thus, a prospective study is needed to explore the potential role of chrono-nutrition practices in modifying risk factors to delay the transition of MHO to MUO.

OBESITY, METABOLIC SYNDROME AND BIOIMPEDANSOMETRY IN MODERN PEDIATRIC PRACTICE (LITERATURE REVIEW)

The review presents current literature data on the prevalence of obesity and metabolic syndrome in children. According to the WHO’s prognosis, over 25% of children will be overweight and obese and about 7% of children will have metabolic syndrome in Europe by 2025. Long-lasting improper diet combined with reduced physical activity, with daily caloric food value exceeding vital energy requirements, is the main cause of excess body weight and obesity. It has been presented new, never-before-seen, properties of adipose tissue being the largest endocrine organ, which contains receptors for many hormones and produces its own peptide hormones-adipokines (leptin, adiponectin, resistin, tumor necrosis factor-alpha, etc.). It has been indicated that patients suffering from obesity and metabolic syndrome have impaired incretin effect (glucose-dependent insulin stimulation, decreased glucagon secretion) in response to the action of incretin hormones (glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide) caused by acquired receptor defects . It has been noted that differentiation of mesenchymal stem cells into two pools of cells (Myf5-positive and Myf5-negative) is subsequently completed with their transformation into white, brown and previously unknown beige adipose tissue. Metabolically healthy obesity, the phenotype of which is mainly due to the gene expression in the CNS, and Metabolically Unhealthy Obesity, the phenotype of which is due to the expression of peripheral tissue genes, are the most common phenotypes of polygenic obesity. It has been emphasized that Metabolically Unhealthy Obesity is considered by some authors to be the modernized name of the metabolic syndrome. The metabolic syndrome is known to be pathogenetically associated with obesity, hypertension, dyslipidemia, impaired glucose tolerance, and type 2 diabetes mellitus. It has been noted that until recently there were no uniform criteria for determining the metabolic syndrome in children. Nowadays, researchers keep to the criteria for Metabolically Unhealthy Оbesity in children, recommended by the American Association of Clinical Endocrinologists and the American College of Endocrinologists (AACE / ACE), 2014; and the European Society of Endocrinologists (ESE) and the Pediatric Endocrinology Society (PES), 2017. Early diagnosis and timely correction of obesity and metabolic syndrome is impossible without modern innovative medical technologies. The use of bioimpedancemetry for the diagnosis of total fat, visceral fat and metabolic age makes it possible to accurately diagnose visceral obesity, which is not recognized by body mass index, and timely administer a personalized lifestyle correction. Consequently, the widespread introduction of bioimpedancemetric analysis in paediatric practice will facilitate the early primary and secondary prophylaxis and development of comprehensive personalized treatment programs for obesity and metabolic syndrome in children.

Milestones in Molecular Mechanisms of Adipogenesis and Adipose Tissue Plasticity

This review focuses on the problem of adipogenesis mechanisms and the biological role of adipose tissue (AT) in the human body. Over the past decades, various types of adipocytes have been identified and characterized—white, brown, beige, yellow, and pink. An important feature of AT is a high plasticity and the ability to transdifferentiate and de-differentiate into another cell type. In this case, the pathway of transformation mostly depends on adipocytes’ cellular and metabolic microenvironment. The mechanisms of adipogenesis and the ways of its regulation remain not fully understood. The principal role in the terminal differentiation of preadipocytes is assigned to PPARγ and receptors activated by bone morphogenetic proteins, insulin, and cortisol. However, in chronic inflammation, adipogenesis is suppressed and old adipocytes increase the production of proinflammatory cytokines, which leads to the death of inflamed cells and hypertrophy of neighboring adipocytes. Thus, disruption of adipogenesis, premature aging of white adipocytes, perturbations in the metabolic and cellular microenvironment of preadipocytes, and early apoptosis of fat cells cause the development of insulin resistance and metabolically unhealthy obesity.

Association of leptin receptor gene polymorphisms and meta-inflammation markers with metabolically unhealthy obesity in children

The aim: to study the contribution of single-nucleotide polymorphisms (SNP) of the leptin receptor (LEPR) gene and meta-inflammation markers to the formation of metabolically unhealthy obesity (MUO) in children. Materials and methods. A total of 109 obese children aged 6–18 years were examined. Based on the recommendations of the National Heart, Lung, and Blood Institute (NHLBI), 2 observation groups were formed. The main group (n = 56) was represented by patients with MUO. The control group (n = 53) comprised children with metabolically healthy obesity (MHO). Serum levels of interleukin-1β (IL-1β) were measured using a chemiluminescent immunoassay (CLIA) method, interleukin-6, leptin, adiponectin – by enzyme-linked immunosorbent assay (ELISA) and the serum level of C-reactive protein were quantified by latex turbidimetric method (Synevo, Ukraine). The method of next-generation sequencing (NGS) (CeXGat, Germany) was used to identify LEPR SNP. Statistical methods were used: analysis of variance, Spearman’s correlation analysis and multiple discriminant analysis. Results. In obese children aged 6 to 18 years, there was an increase in pro-inflammatory adipokines IL-6 and leptin and a decrease in anti-inflammatory adiponectin. Statistically significant changes in these indicators were more expressed in the main group: IL-6 – 7.4 ± 0.5 pg/ml (ρ = 0.65; P ≤ 0.001); adiponectin – 3.9 ± 0.8 μg/ml (ρ = -0.27; P = 0.007) among all the children examined, leptin in girls – 47.8 ± 4.4 ng/ml (ρ = -0.28; P = 0.003) compared with the results of patients in the control group: IL-6 – 4.3 ± 0.3 pg/ml, adiponectin – 7.7 ± 2.4 μg/ml, leptin in girls – 32.5 ± 4.3 ng/ml, P ≤ 0.05. The most important in the development of MUO were the following SNP of the LEPR gene: rs3790435 (CiMUO = 0.939), rs2186248 (CiMUO = 0.862), P < 0.05. A strong correlation was found between MUO and serum IL-6 level (ρ = 0.7), LEPR SNP rs3790435 (ρ = 0.7), basal hyperinsulinemia (ρ = 0.72); Р ≤ 0.001. The risk of IL-6-dependent meta-inflammation in the presence of SNP rs3790435 of the LEPR gene: OR = 17.11; 95 % CI 2.8–20.4. Conclusions. Meta-inflammation in MUO is IL-6-dependent. Among the 10 SNPs of the LEPR gene that we identified, SNP rs3790435 of the LEPR gene has a strong association with the formation of MUO. SNP rs2186248 LEPR was described by us for the first time when it was found in 94.1 % of obese children, but it was characterized by the presence of a weak association with MUO.