Maternal glucose homeostasis during pregnancy in women with overweight or obesity and offspring metabolic health.

Gestational diabetes mellitus (GDM) adversely affects offspring glucose homeostasis and risk of developing obesity. Here, we examined the association between glycemia in pregnant women with overweight or obesity without GDM and offspring metabolic health. Maternal fasting glucose concentrations and glucose 2-h after an oral glucose tolerance test (OGTT) were measured in 208 women with a pre-pregnancy body mass index (BMI) of 28-45 kg/m2 without GDM. Offspring outcomes were collected at birth, 3, and 5 years of age. Linear mixed models with time as fixed factor and subject ID as random effects were used for analysis. No associations were found between maternal fasting or 2-h glucose concentrations with offspring glucose and insulin concentrations from birth to 5 years of age. However, maternal fasting glucose in GW 28 and 36, and 2-h OGTT glucose in GW 28 were positively associated with C-peptide concentration at birth. Maternal fasting glucose concentrations in GW 28 and 36 were positively associated with weight-for-length, and maternal fasting glucose in GW 36 was associated with BMI z-score at birth. In summary, blood glucose in pregnant women with overweight or obesity is positively associated with offspring C-peptide concentration, weight-for-length, and BMI z-score at birth, even in the absence of GDM.

Effects of dietary interventions and intermittent fasting on HDL function in obese individuals with T2DM: a randomized controlled trial.

BACKGROUND: Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM. METHODS: Before the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants' glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA. RESULTS: Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance. CONCLUSIONS: A balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality. TRIAL REGISTRATION: The study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070.

The Role of 11-Oxygenated Androgens and Endocrine Disruptors in Androgen Excess Disorders in Women.

Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are androgen excess disorders requiring the determination of classic androgen levels for diagnosis. 11-oxygenated androgens have high androgenic potential, yet their clinical value in those disorders is not clear. Additionally, the role of endocrine disruptors (EDs), particularly in IH, remains understudied. We analyzed 25 steroids and 18 EDs in plasma samples from women with IH, PCOS, and controls using LC-MS/MS. Cytokine levels and metabolic parameters were assessed. Comparisons included non-obese women with PCOS (n = 10), women with IH (n = 12) and controls (n = 20), and non-obese versus obese women with PCOS (n = 9). Higher levels of 11-oxygenated androgens were observed in women with PCOS compared to those with IH, but not controls. Conversely, 11-oxygenated androgen levels were lower in women with IH compared to controls. Cytokine levels did not differ between women with IH and controls. Bisphenol A (BPA) levels were higher in obese women with PCOS compared to non-obese women with PCOS. Bisphenol S occurrence was higher in women with PCOS (90%) compared to controls (65%) and IH (50%). Significant correlations were found between androgens (11-ketotestosterone, androstenedione, testosterone) and insulin and HOMA-IR, as well as between immunomodulatory 7-oxygenated metabolites of DHEA and nine interleukins. Our data confirms that PCOS is a multiendocrine gland disorder. Higher BPA levels in obese women might exacerbate metabolic abnormalities. IH was not confirmed as an inflammatory state, and no differences in BPA levels suggest BPA does not play a role in IH pathogenesis.

Exploring the Impact of Astaxanthin Supplementation in Conjunction with a 12-Week CrossFit Training Regimen on Selected Adipo-Myokines Levels in Obese Males.

OBJECTIVE: Obesity is associated with an exacerbated metabolic condition that is mediated through impairing balance in the secretion of some adipo-myokines. Therefore, the objective of the present study was to explore the impact of astaxanthin supplementation in conjunction with a 12-week CrossFit training regimen on some selected adipo-myokines, insulin insensitivity, and serum lipid levels in obese males. MATERIAL AND METHODS: This study is a randomized control trial design; 60 obese males were randomly divided into four groups of 15, including the control group (CG), supplement group (SG), training group (TG), and combined training and supplement group (TSG). The participants were subjected to 12 weeks of astaxanthin (AST) supplementation [20 mg/d capsule, once/d] or CrossFit training or a combination of both interventions. The training regimen comprised 36 sessions of CrossFit, each lasting 60 min, conducted three times per week. The metabolic indices, body composition, anthropometrical, cardio-respiratory, and also some plasma adipo-myokine factors, including decorin (DCN), activin A, myostatin (MST), transforming growth factor (TGF)-ß1, and follistatin (FST), were examined 12 and 72 h before the initiation of the main interventional protocols, and then 72 h after the final session of the training protocol. RESULTS: There was no significant difference in the baseline data between the groups (p > 0.05). There were significant interactions between group x time for DCN (η2 = 0.82), activin A (η2 = 0.50), FST (η2 = 0.92), MST (η2 = 0.75), and TGFB-1 (η2 = 0.67) (p < 0.001 for all the variables). Significantly changes showed for DCN in TSG compared to TG and SG and also TG compared to SG (p = 0.0001); for activin A in SG compared to TG (p = 0.01) and TSG (p = 0.002); for FST in SG compared to TG and TSG (p = 0.0001), also in TSG compared to TG (p = 0.0001); for MST in SG, TG, and TSG compared to CG (p = 0.0001) and also in TSG compared to SG (p = 0.0001) and TG (p = 0.001); for TGFB-1 in SG, TG, and TSG compared to CG (p = 0.0001) and also TSG compared to SG (p = 0.0001) and TG (p = 0.001). CONCLUSIONS: The 12-week CrossFit training concurrent with AST supplementation reduced anthropometric and metabolic factors and also serum lipid levels while producing positive changes in body composition and cardiovascular factors. Increased FST and DCN and reduced activin A, MST, and TGF-ß1 were other affirmative responses to both interventions.

Relationships between HDL subpopulation proteome and HDL function in overweight/obese people with and without coronary heart disease.

BACKGROUND AND AIMS: The structure-function relationships of high-density lipoprotein (HDL) subpopulations are not well understood. Our aim was to examine the interrelationships between HDL particle proteome and HDL functionality in subjects with and without coronary heart disease (CHD). METHODS: We isolated 5 different HDL subpopulations based on charge, size, and apolipoprotein A1 (APOA1) content from the plasma of 33 overweight/obese CHD patients and 33 age-and body mass index (BMI)-matched CHD-free subjects. We measured the relative molar concentration of HDL-associated proteins by liquid chromatography tandem mass spectrometry (LC-MS/MS) and assessed particle functionality. RESULTS: We quantified 110 proteins associated with the 5 APOA1-containing HDL subpopulations. The relative molar concentration of these proteins spanned five orders of magnitude. Only 10 proteins were present in >1% while 73 were present in <0.1% concentration. Only 6 of the 10 most abundant proteins were apolipoproteins. Interestingly, the largest (α-1) and the smallest (preß-1) HDL particles contained the most diverse proteomes. The protein composition of each HDL subpopulation was altered in CHD cases as compared to controls with the most prominent differences in preß-1 and α-1 particles. APOA2 concentration was positively correlated with preß-1 particle functionality (ABCA1-CEC/mg APOA1 in preß-1) (R2 = 0.42, p = 0.005), while APOE concentration was inversely correlated with large-HDL particle functionality (SRBI-CEC/mg APOA1 in α-1+α-2) (R2 = 0.18, p = 0.01). CONCLUSIONS: The protein composition of the different HDL subpopulations was altered differentially in CHD patients. The functionality of the small and large HDL particles correlated with the protein content of APOA2 and APOE, respectively. Our data indicate that distinct particle subspecies and specific particle associated proteins provide new information about the role of HDL in CHD.

Short- and long-term effects of concurrent aerobic and resistance training on circulating irisin levels in overweight or obese individuals: a systematic review and meta-analysis of randomized controlled trials.

Background: Concurrent training (CT) is emerging as a practical and effective approach to enhance body composition, cardiovascular function, and muscle mass, thereby elevating overall individual health. This study aims to systematically investigate the effects of short- and long-term concurrent aerobic and resistance training on circulating irisin levels in overweight or obese individuals. Methodology: The electronic databases, including China National Knowledge Infrastructure, PubMed, Embase, Wan Fang Database, and Web of Science, were systematically searched for articles on "concurrent training" and "irisin" published from their inception to 30 November 2023. The pooled effect size was determined using standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs). The study protocol received registration with the International Prospective Register of Systematic Reviews (CRD42023494163). Results: All nine studies, encompassing a total of 264 participants, were randomized controlled trials and met the eligibility criteria. Results indicate that short- and long-term concurrent training moderately increased circulating irisin levels compared to the control group (SMD = 0.56, 95% CI [0.33-0.80], p = 0.00; I 2 = 36.6%, heterogeneity p = 0.106). Subgroup analyses revealed that both equal to or less than 10 weeks (SMD = 0.78, 95% CI [0.18-1.37], p = 0.01; I 2 = 62.3%, heterogeneity p = 0.03) and more than 10 weeks (SMD = 0.45, 95% CI [0.14-0.76], p = 0.00; I 2 = 0%, heterogeneity p = 0.54) of concurrent training significantly increased circulating irisin levels in overweight or obese individuals. There were no significant between-group differences (I 2 = 0%, p = 0.34). Additionally, concurrent training significantly increased irisin levels in overweight or obese participants (SMD = 1.06, 95% CI [0.34-1.78], p = 0.00; I 2 = 50.6%, heterogeneity p = 0.13) and in type 2 diabetes patients (SMD = 0.70, 95% CI [0.30-1.10], p = 0.00; I 2 = 0%, heterogeneity p = 0.99). However, no significant effect was observed in patients with metabolic syndrome (SMD = 0.21, 95% CI [-0.25-0.68], p = 0.37; I 2 = 38.7%, heterogeneity p = 0.18). There were significant between-group differences (I 2 = 53.9%, p = 0.11). Lastly, concurrent training significantly increased circulating irisin levels in overweight or obese individuals aged 45-60 years (SMD = 0.56, 95% CI [0.25-0.86], p = 0.00; I 2 = 6.5%, heterogeneity p = 0.38), and a significant increase in irisin levels was observed 12 h post-intervention (SMD = 0.70, 95% CI [0.35-1.05], p = 0.00; I 2 = 0%, heterogeneity p = 0.74). However, none of the above categorical variables showed significant between-group differences. Conclusions: Short- and long-term concurrent training can effectively improve circulating irisin levels in overweight or obese individuals. However, the effects of short- and long-term concurrent training should consider the participants' health status, age, and the timing of post-exercise measurements to maximize health benefits.

The association of triglyceride-glucose index and combined obesity indicators with chest pain and risk of cardiovascular disease in American population with pre-diabetes or diabetes.

Aim: To investigate the correlation of the triglyceride-glucose (TyG) index and its combined obesity indicators with chest pain and cardiovascular disease (CVD) in the pre-diabetes and diabetes population. Methods: This cross-sectional investigation encompassed 6488 participants with diabetes and pre-diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016. The association of the TyG and combined obesity index with chest pain and CVD was investigated using weighted logistic regression models and restricted cubic spline (RCS) analysis. The receiver operating characteristic (ROC) curve analysis was performed to compare different indicators. Results: In multivariate logistic regression fully adjusted for confounding variables, our analyses revealed significant associations between TyG, TyG-BMI, TyG-WC, and TyG-WHtR and chest pain, with adjusted ORs (95% CI) of 1.21 (1.05, 1.39), 1.06 (1.01, 1.11), 1.08 (1.04, 1.14), and 1.27 (1.08, 1.48), respectively. For total-CVD, the adjusted ORs (95% CI) were 1.32 (1.08, 1.61), 1.10 (1.03, 1.17), 1.13 (1.06, 1.19), and 1.63 (1.35, 1.97), respectively, among which TyG, TyG-WC, and TyG-WHtR present curvilinear associations in RCS analysis (all P-nonlinear < 0.05). Furthermore, the ROC curve showed that TyG-WC had the most robust predictive efficacy for total-CVD, coronary heart disease (CHD), and myocardial infarction (MI), while TyG-WHtR had the best predictive ability for angina and heart failure. Conclusion: There are significant associations of TyG and its related indicators with chest pain and total-CVD among the pathoglycemia population. TyG-WC and TyG-WHtR demonstrated superior predictive capability for the incidence of cardiovascular events.

The Release of Lipolytic Hormones during Various High-Intensity Interval and Moderate-Intensity Continuous Training Regimens and Their Effects on Fat Loss.

To investigate the release of lipolytic hormones during various high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), and their effects on fat loss. 39 young women categorized as obese (with a body fat percentage (BFP) ≥30%) were randomly allocated to one of the following groups: all-out sprint interval training (SIT, n =10); supramaximal HIIT (HIIT120, 120%V̇O2peak, n = 10); HIIT (HIIT90, 90%V̇O2peak, n = 10), or MICT, (60%V̇O2peak, n = 9) for a twelve-week observation period consisting of 3 to 4 exercise sessions per week. Serum epinephrine (EPI) and growth hormone (GH) were measured during the 1st, 20th, and 44th training sessions. Body weight (BW), body mass index (BMI), whole-body fat mass (FM) and BFP were assessed pre- and post-intervention. Following the 1st and 20th sessions, significant increases in EPI (p < 0.05) were observed post-exercise in HIIT120 and HIIT90, but not in SIT and MICT. In the 44th session, the increased EPI was found in SIT, HIIT120, and HIIT90, but not in MICT (p < 0.05). For the GH, a significant increase was observed post-exercise in all groups in the three sessions. The increased EPI and GH returned to baselines 3 hours post-exercise. After the 12-week intervention, significant reductions in FM and BFP were found in all groups, while reductions in BW and BMI were only found in the SIT and HIIT groups. Greater reductions in FM and BFP, in comparison to MICT, were observed in the SIT and HIIT groups (p < 0.05). 12-week SIT, HIIT120, and HIIT90, in comparison to MICT, were more efficacious in fat reduction in obese women, partly benefiting from the greater release of lipolytic hormones during training sessions.

Cholesterol to saturated fat index (CSI), metabolic parameters and inflammatory factors among obese individuals.

BACKGROUND: The role of dietary fat quality in promotion of cardiovascular diseases is studies before. However, the results are inconsistent. Recently, cholesterol to saturated fatty acid index (CSI) is suggested as a novel indicator of the atherogenicity and thrombogenicity potential of a diet. However, due to limited number of studies, in the current cross-sectional study, we aimed to evaluate the role of CSI in metabolic and inflammatory response among obese individuals. METHODS: In the current cross-sectional study 488 obese individuals aged 18-50 years old were involved in volunteer based invitation from outpatient obesity clinics. Subjects underwent anthropometric assays including weight, height, waist circumference (WC) and body composition and their fasting blood sample were obtained for biochemical assessments including blood sugar, serum lipids, hs-CRP and IL-6 concentrations by commercial kits. Physical activity was also assessed by short form of international physical activity questionnaire (IPAQ). RESULTS: According to our results, being at the top tetile of CSI was associated with higher anthropometric indices including weight, height, WC, FFM, and basal metabolic rate (BMR) compared with those at the lowest tertile (P < 0.05). Similarly, those at the highest category of CSI had significantly higher levels of serum glucose and hs-CRP both in crude and adjusted models in ANCOVA and in multinomial logistic regression models (P < 0.05). CONCLUSION: In the current study, for the first time, we identified the possible triggering role of dietary cholesterol to saturated fat index in increasing serum glucose and hs-CRP levels. due to cross-sectional design of the current study, causal inference is impossible. Further studies will help for better scientific justification.

Serum selenium accelerates the development of metabolic disorders in a metabolically healthy obese U.S. population: a retrospective cross-sectional analysis of a population-based study from the NHANES (2011-2018).

Background: Obesity represents a significant risk factor for the development of metabolic abnormalities. However, it is not inevitable that all individuals with obesity will develop these disorders. Selenium has been demonstrated to play a role in maintaining metabolic homeostasis in vivo, with the ability to regulate relevant signaling pathways involved in glucose and lipid metabolism processes. Previous studies have indicated that selenium concentrations in obese individuals are higher than those reported in the general population. These findings the question of whether altered selenium concentrations may act as important triggers for accelerating metabolic imbalances in the obese population. The aim of this study was to examine the potential correlation between serum selenium concentrations and the risk of developing metabolic abnormalities in individuals with obesity. Methods: The present study included 6,125 participants from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) who were aged between 20 and 80 years, with a body mass index (BMI) of 30 kg/m2 or greater, and met the inclusion and exclusion criteria. Weighted generalized linear regression analyses were conducted to evaluate the associations between serum selenium concentrations and the conversion of metabolically healthy obesity (MHO) to metabolically unhealthy obesity (MUO). A generalized additive model (GAM) and a two-piecewise linear regression model were employed to investigate the saturation threshold effect between selenium and MUO. The correlation between different selenium concentration intervals and metabolic diseases was evaluated by categorizing selenium concentrations according to the saturation threshold. Furthermore, this study investigated the correlation between serum selenium and lipid concentrations in obese females and between serum selenium and blood pressure in obese males. Results: The weighted prevalence of MUO in the study population was 48.35%. After rigorous adjustment for sociodemographic, physical, and laboratory test covariates, the weighted odds ratio (OR) of MUO increased by 44% for every 1 µM increase (approximately 78.74 µg) in the serum selenium concentration (weighted OR=1.44; 95% CI=1.09 - 1.91; P=0.018). Second, GAM analysis and saturation threshold analyses revealed an inverted U-shaped relationship between serum selenium and metabolic abnormalities in males, with a corresponding inflection point (K) of 2.82 µM. When the serum selenium concentration was below the K-value, the effects of serum selenium were mainly on blood pressure, especially diastolic blood pressure (DBP) (weighted ß: 3.34; 95% CI= 0.25 - 6.44; P=0.038). Conversely, the correlation between the serum selenium concentrations and metabolic homeostasis imbalance in females was linear. When the selenium concentration exceeded 2.12 µM, the increase in selenium content was accompanied by increases in total cholesterol (TC, weighted ß=0.54, 95% CI=0.32 - 0.76; P=0.000) and triglyceride (TG, weighted ß=0.51, 95% CI=0.27 - 0.75; P=0.000) concentrations. Conclusions: The findings of our study indicate that selenium supplementation strategies for individuals with obesity should be tailored to the sex of the individual. In females, serum selenium concentration above the saturation threshold primarily facilitates the transition from MHO to MUO by influencing alterations in serum lipid metabolism. Maintaining selenium concentrations below the threshold levels is highly important for preventing the conversion of MHO to MUO. In males, serum selenium concentrations above the threshold were found to be effective in preventing an elevation in blood pressure, particularly in improving systolic blood pressure (SBP). Nevertheless, serum selenium concentrations below the threshold are linked to an increased risk of hypertension in obese individuals, particularly those with elevated diastolic blood pressure (DBP). Further research is needed to elucidate the optimal serum selenium concentration that exerts deleterious effects on blood pressure.

Obesity influencing circulating levels of nutrients: Evidence from Mendelian randomization study.

Observational studies have established that obesity is associated with nutritional deficiencies, but the exact causality remains uncertain. Thus, this Mendelian randomization (MR) study aimed to identify the causal associations between obesity and circulating levels of nutrients. Single-nucleotide polymorphisms associated with obesity (body mass index and waist-hip ratio), were extracted from a genome-wide association study of 694,649 European ancestry. Summary-level data for minerals (copper, selenium, zinc, calcium, magnesium, and potassium), and vitamins (folate, vitamins A, C, E, B6, and B12), albumin were obtained from the publicly available integrative epidemiology unit OpenGWAS database psychiatric genomics consortium. Inverse-variance weighted method several sensitivity analyses were conducted. Genetically predicted higher body mass index significantly decreased circulating levels of magnesium (ß = -0.07, 95% confidence interval [CI]: -0.10 to -0.03, P = 1.47 × 10-4), folate (ß = -0.07, 95% CI: -0.10 to -0.04, P = 5.61 × 10-5), vitamin A (ß = -0.11, 95% CI: -0.14 to -0.07, P = 3.10 × 10-9), vitamin E (ß = -0.10, 95% CI: -0.13 to -0.06, P = 1.84 × 10-8), albumin (ß = -0.15, 95% CI: -0.17 to -0.12, P = 9.89 × 10-28); whereas genetically predicted higher waist-hip ratio decreased circulating levels of magnesium (ß = -0.07, 95% CI: -0.11 to -0.02, P = 1.87 × 10-3), folate (ß = -0.07, 95% CI: -0.11 to -0.03, P = 9.87 × 10-4), vitamin C (ß = -0.08, 95% CI: -0.12 to -0.04, P = 2.40 × 10-4), albumin (ß = -0.08, 95% CI: -0.11 to -0.04, P = 3.72 × 10-5). The study supports a causal effect of obesity on lower circulating levels of nutrients. Our findings highlight the necessity of adjuvant nutrients in obesity management.

Adiponectin Resistance in Obesity: Adiponectin Leptin/Insulin Interaction.

The adiponectin (APN) levels in obesity are negatively correlated with chronic subclinical inflammation markers. The hypertrophic adipocytes cause obesity-linked insulin resistance and metabolic syndrome. Furthermore, macrophage polarization is a key determinant regulating adiponectin receptor (AdipoR1/R2) expression and differential adiponectin-mediated macrophage inflammatory responses in obese individuals. In addition to decrease in adiponectin concentrations, the decline in AdipoR1/R2 messenger ribonucleic acid (mRNA) expression leads to a decrement in adiponectin binding to cell membrane, and this turns into attenuation in the adiponectin effects. This is defined as APN resistance, and it is linked with insulin resistance in high-fat diet-fed subjects. The insulin-resistant group has a significantly higher leptin-to-APN ratio. The leptin-to-APN ratio is more than twofold higher in obese individuals. An increase in expression of AdipoRs restores insulin sensitivity and ß-oxidation of fatty acids via triggering intracellular signal cascades. The ratio of high molecular weight to total APN is defined as the APN sensitivity index (ASI). This index is correlated to insulin sensitivity. Homeostasis model of assessment (HOMA)-APN and HOMA-estimated insulin resistance (HOMA-IR) are the most suitable methods to estimate the metabolic risk in metabolic syndrome. While morbidly obese patients display a significantly higher plasma leptin and soluble (s)E-selectin concentrations, leptin-to-APN ratio, there is a significant negative correlation between leptin-to-APN ratio and sP-selectin in obese patients. When comparing the metabolic dysregulated obese group with the metabolically healthy obese group, postprandial triglyceride clearance, insulin resistance, and leptin resistance are significantly delayed following the oral fat tolerance test in the first group. A neuropeptide, Spexin (SPX), is positively correlated with the quantitative insulin sensitivity check index (QUICKI) and APN. APN resistance together with insulin resistance forms a vicious cycle. Despite normal or high APN levels, an impaired post-receptor signaling due to adaptor protein-containing pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1)/APPL2 may alter APN efficiency and activity. However, APPL2 blocks adiponectin signaling through AdipoR1 and AdipoR2 because of the competitive inhibition of APPL1. APPL1, the intracellular binding partner of AdipoRs, is also an important mediator of adiponectin-dependent insulin sensitization. The elevated adiponectin levels with adiponectin resistance are compensatory responses in the condition of an unusual discordance between insulin resistance and APN unresponsiveness. Hypothalamic recombinant adeno-associated virus (rAAV)-leptin (Lep) gene therapy reduces serum APN levels, and it is a more efficient strategy for long-term weight maintenance.

[Features of the relationship of intestinal microbiota indicators with clinical and biochemical parameters in obese young people].

BACKGROUND: The prevalence of obesity is rising dramatically worldwide. Recently, there is increasing evidence linking obesity with the functional state of the intestinal microbiota. The understanding of this relationship may provide new approaches to the treatment of obesity by manipulating the qualitative and quantitative parameters of intestinal bacterial-fungal associations. AIM: To study the features of the qualitative and quantitative composition of the colon microbiota and to evaluate associations with anamnestic, anthropometric and biochemical parameters in young obese patients. MATERIALS AND METHODS: A single-center, cross-sectional, single-stage, controlled study was conducted with the participation of 118 young people, of whom 87 were obese, and 31 people with normal body weight formed the control group. All participants underwent a biochemical blood test (total cholesterol, high-density lipoproteins, low-density lipoproteins, very low-density lipoproteins, triglycerides, uric acid, glucose, glycated hemoglobin, C-reactive protein), as well as an assessment of the state of the colon microbiota using polymerase chain reaction in real time using a set of Colonoflor-16 (premium) reagents. The Microsoft Excel 2010 and IBM SPSS Statistics 26.0 application software package was used for statistical calculations. The results were evaluated as statistically significant at a level of p<0.05. RESULTS: Analyzing the result of Colonoflor-16 premium, the discrepancy between the obtained data of the control group and the reference values of the analysis was revealed. There was a clear tendency to decrease the content of Lactobacillus spp and Bifidobacterium spp in the obesity group. In addition, in comparison with the control group (10.3%), in the obesity group Fusobacterium nucleatum significantly prevailed (37.6%) (p=0.005), with a significant decrease in the bacteria Faecalibacterium prausnitzii (p=0.030), and an increase in the bacteria Prevotella spp (p=0.029). A lot of associations of representatives of the colon microbiota with the most important anamnestic, anthropometric and biochemical parameters were revealed in young obese patients. CONCLUSION: There is a redistribution of microbiota phylotypes characterized by a decrease in apathogenic microorganisms and the appearance and increase of opportunistic and pathogenic microorganisms, which generally indicates the formation of the pro-inflammatory potential of dominants and associates in young obese patients. The presence of statistically significant correlations strongly indicates of existence of close and diverse relationships between the quantitative and qualitative parameters of the microbiota and the metabolic parameters of patients.

Association of circulating visfatin level and metabolic fatty liver disease: An updated meta-analysis and systematic review.

BACKGROUND: The rate of incidence of metabolic dysfunction-related fatty liver disease (MAFLD) has rapidly increased globally in recent years, but early diagnosis is still a challenge. The purpose of this systematic review and meta-analysis is to identify visfatin for early diagnosis of MAFLD. METHODS: We strictly adhered to the relevant requirements of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic search was conducted in 7 sources (PubMed, Embase, Cochrane Library, CNKI, Wanfang, CBM, and ClinicalTrials.gov) until February 2024. The meta-analysis was performed using Stata 12. Outcomes were expressed in the form of standardized mean difference (SMD) and 95% confidence interval and were analyzed using meta-analysis. RESULTS: The results showed that there was no significant difference in circulating visfatin levels between patients with MAFLD and controls (SMD = 0.13 [-0.34, 0.60]). However, the outcomes indicated that the level of circulating visfatin was significantly higher in MAFLD patients in the Middle Eastern subgroup (SMD = 0.45 [0.05, 0.85]) and in the obese patient subgroup (SMD = 1.05 [0.18, 1.92]). No publication bias was detected, and sensitivity analysis confirmed the stability of the outcomes. CONCLUSION: The serum visfatin levels of MAFLD patients did not differ significantly from those of controls. However, visfatin concentrations in serum were statistically higher within Middle Eastern or obese MAFLD patients compared to controls. There is a need for further research to investigate visfatin's potential as a biomarker for MAFLD.

Association of serum calcium and metabolically healthy obese in US adults: a cross-sectional study.

OBJECTIVES: The relationship between serum calcium and occurrence of MHO (metabolically healthy obesity) and MUNO (metabolically unhealthy non-obesity) remains unclear, and distinguishing these two phenotypes is difficult within primary healthcare units. This study explores that relationship. METHODS: This survey included 28590 adults from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. Obesity phenotypes were categorized based on BMI and presence or absence of metabolic syndrome components. Weighted multivariate logistic regression analyses were used to assess the association between serum calcium levels and the obesity phenotype. Restricted cubic spline analysis characterized dose-response relationships, and stratified analyses explored these relationships across sociodemographic and lifestyle factors. RESULTS: The overall prevalence of MHO and MUNO were 2.6% and 46.6%, respectively. After adjusting for covariates, serum calcium exhibited a negative association with MHO [OR (95%): 0.49 (0.36,0.67), p < 0.001], while exhibiting a positive association with MUNO [OR (95%): 1.48 (1.26,1.84), p < 0.001]. Additionally, we found a non-linear association between serum calcium levels and the incidences of MHO and MUNO. Stratified analyses demonstrated a strong negative correlation between serum calcium levels and MHO occurrence across various subgroups. There was no significant interaction between calcium and stratified variables except sex; the association between calcium and the occurrence of MHO was remarkable in female patients. Meanwhile, the predictive ability of serum calcium level for the occurrence of MUNO among all patients was consistent across various subgroups. There was a significant interaction between calcium level and stratified variables based on age, sex, race, and smoking status; the association was remarkable in older (≥ 40 years old), white, none or less smoking, and female patients. CONCLUSIONS: A significant correlation was identified between serum calcium levels and MHO or MUNO. The findings suggest that serum calcium levels may serve as an indicator for more accurate assessment and diagnosis of MUNO and MHO, especially among individuals with abdominal obesity.

Serum calcium levels exhibited an inverse relationship with metabolically healthy obesity (MHO) and a positive relationship with metabolically unhealthy non-obese (MUNO).A nonlinear association exists between serum calcium levels and the incidence of both MHO and MUNO.Serum calcium has the potential to enhance evaluation and screening for MUNO or MHO in the general US adult population.

Comparison of leptin and estrone levels between normal body mass index and obese menopausal women.

Postmenopausal women often experience hormonal changes and shifts in fat composition, affecting weight gain and obesity. Understanding the link between hormones, especially estrogen and leptin, is key to managing weight and lowering disease risk in menopausal women. The aim of this study was to compare the levels of leptin and estrone in menopausal women with normal weight and obesity. A cross-sectional study was conducted on menopausal women, either normal body mass index (BMI) or obese, at H. Adam Malik General Hospital, Medan, Indonesia. Blood samples were collected to measure leptin and estrone levels using the enzyme-linked immunosorbent assay (ELISA) method. The differences in leptin levels between groups were analyzed using the Wilcoxon test, while the correlation between BMI and leptin was examined using the Pearson correlation test. The disparity in estrone levels in both groups was analyzed using the Mann-Whitney test and the correlations between variables were assessed using the Spearman or Pearson correlation tests as appropriate. The mean leptin levels in normal BMI and obesity groups were 17.73±4.96 and 25.46±12.95 ng/mL, respectively, and were statistically different (p=0.006). The mean estrone levels in menopausal women with normal BMI and obesity were 943.23±391.79 and 851.38±282.23 ng/mol, respectively and were not statistically different (p=0.564). A significant positive correlation was found between BMI and leptin level (r=0.59; p<0.001), while BMI and estrone were not significantly correlated (r=0.083; p=0.559). In conclusion, leptin level was significantly different between BMI groups and had a strong positive correlation with BMI. This finding could be an important insight in body weight management and disease risk prevention in menopausal women.

Associations of Adipokine Levels With Levels of Remnant Cholesterol: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. METHODS AND RESULTS: We studied 1791 MESA (Multi-Ethnic Study of Atherosclerosis) participants who took part in an ancillary study on body composition with adipokine levels measured (leptin, adiponectin, and resistin) at either visit 2 or visit 3. RC was calculated as non-high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol, measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed-effects models were used to assess the cross-sectional and longitudinal associations between adipokines and log-transformed levels of RC. Mean±SD age was 64.5±9.6 years; mean±SD body mass index was 29.9±5.0 kg/m2; and 52.0% were women. In fully adjusted cross-sectional models that included body mass index, diabetes, low-density lipoprotein cholesterol, and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.6% (95% CI, 12.2-16.9) lower RC. With each 1-unit increment in leptin and resistin, there was 4.8% (95% CI, 2.7-7.0) and 4.0% (95% CI, 0.2-8.1) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5 (interquartile range, 4-8) years. CONCLUSIONS: Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for body mass index and low-density lipoprotein cholesterol.

Higher serum myostatin levels are associated with lower insulin sensitivity in adults with overweight/obesity.

Myostatin inhibition improves insulin sensitivity in preclinical and clinical models; however, studies investigating the relationship between serum myostatin levels and insulin sensitivity are discrepant. Sensitive and specific myostatin LC-MS/MS assays are now available to accurately assess serum myostatin level in vivo. We sought to determine whether higher serum myostatin levels are independently associated with lower insulin sensitivity in adults with overweight/obesity. Participants included 74 adults, 20-65 years old, BMI ≥25 kg/m2 without type 2 diabetes. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry; visceral adipose tissue (VAT) was measured by computed tomography. Main outcome measures were serum myostatin levels (LC-MS/MS) and insulin sensitivity (Matsuda index). Mean age was 48 ± 12 years, and BMI was 33.1 ± 5.6 kg/m2 (mean ± SD). Men had higher mean serum myostatin levels versus women (8.3 ± 1.9 vs. 7.2 ± 1.9 ng/mL, p = 0.01) and higher serum myostatin levels were associated with higher ALM (R = 0.34, p = 0.003). Higher serum myostatin levels were associated with lower Matsuda index (R = -0.44, p = 0.0004), which remained significant after controlling for BMI, VAT, ALM, and sex. In conclusion, higher serum myostatin levels are independently associated with lower insulin sensitivity in adults with overweight/obesity and may be a marker of or play a mechanistic role in the development of insulin resistance.

The determinants of leptin, angiopoietin like 8, and thyroid hormones levels in Saudi females with type 2 diabetes mellitus: A retrospective study.

This study aimed to assess the prevalence of thyroid dysfunction, as measured by hormone levels, in Saudi women with type 2 diabetes mellitus (T2DM). The study will also assess thyroid hormones and leptin, angiopoietin like 8 (ANGPTL8), obesity, and cardiovascular diseases (CVD) in T2D patients. A total of 250 women aged 40 to 60 years with T2DM were retrospectively studied between 2021 and 2022. This research examined medical records for T2DM patients. In this investigation, no T2DM patients had thyroid autoantibodies in their medical records. These patients were chosen for their FT4 and TSH values. All participants were Saudi females with T2DM, aged 54.5 years. Of the 250 participants, 32% had hypothyroidism, 14.8% had hyperthyroidism, and 40.8% (102) had no thyroid disease. Hypothyroidism (7.8 ±â€…0.67 mmol/L) exhibited greater fasting blood glucose (FBG) levels than hyperthyroidism (7.1 ±â€…0.64 mmol/L) (P < .05). Hypothyroid and hyperthyroid females had significant differences in high density lipoprotein-cholestrol (HDL-C), triglycerides, triglyceride glucose (TyG) index, body mass index (BMI), waist circumstance (WC), high-sensitivity C-reactive protein (hs-CRP), leptin, ANGPTL8, insulin resistance (IR), and insulin levels (P < .05). Pearson's correlation test showed that T2DM patients' HDL-C levels were favorably but negatively correlated with leptin and ANGPTL8 levels. In hypothyroidism, thyroid stimulation hormone (TSH) is favorably linked with glycated hemoglobin (HbA1c), triglyscride (TG), TyG index, BMI, WC, leptin, ANGPTL8, hs-CRP, and IR. T2DM is linked to thyroid malfunction, notably hypothyroidism, which correlates positively with TSH. TSH variations due to increasing leptin, ANGPTL8, and TyG index may enhance the risk of insulin resistance diseases, such as obesity and CVD, in Saudi females with T2DM.

Asymmetric dimethylarginine serum concentration in normal weight and obese CKD patients treated with hemodialysis.

INTRODUCTION: Asymmetric dimethylarginine (ADMA), a cardiovascular risk factor, increases in renal failure. The aim of this study was to investigate ADMA levels in normal weight and obese patients on hemodialysis. METHODS: In this cross-sectional study, 43 normal weight and 43 obese patients on regular hemodialysis were examined. Malnutrition-inflammation score (MIS), anthropometry, circulating ADMA, lipid profiles including triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipid ratios, glucose homeostasis parameters, blood pressure, and high-sensitivity C-reactive protein (hs-CRP) were assessed. RESULTS: Serum levels of ADMA were significantly lower in the obese compared to the normal weight patients (10268.2 ± 10092.4 vs. 13765.2 ± 9951.3 ng/l, P = 0.03). At the same time MIS score (6.1 ± 2.4 vs. 10.7 ± 3.2, P < 0.001), systolic blood pressure (119 ± 26.8 vs. 134.2 ± 24.7 mmHg, P = 0.018) and mean arterial pressure (91.3 ± 18.6 vs. 100.9 ± 15.9 mmHg, P = 0.028) were significantly lower in the obese than the normal weight group. Fasting blood glucose (P = 0.045), TG/HDL (P = 0.03), TC/HDL (P = 0.019), and LDL/HDL (P = 0.005) ratios, and hs-CRP (P = 0.015) levels were significantly higher in the obese than in the normal weight group. CONCLUSION: Circulating ADMA was significantly lower in obese than in normal weight patients on hemodialysis, which was concomitant with lower MIS, indicating a better nutritional inflammatory status, and lower blood pressure.