Obese Control Subjects Research Articles

Increasing Body Mass Index Not Associated With Worse Patient-Reported Outcomes After Primary THA or TKA.

As the US obesity epidemic continues to grow, so too does comorbid hip and knee arthritis. Strict body mass index (BMI) cutoffs for total hip and knee arthroplasty (THA and TKA) in the morbidly obese have been proposed and remain controversial, although current American Academy of Orthopaedic Surgeons guidelines recommend a BMI of less than 40 m/kg2 before surgery. This study sought to compare patient-reported outcomes and 30-day complication, readmission, and revision surgery rates after THA or TKA between morbidly obese patients and nonmorbidly obese control subjects. All patients undergoing primary THA and TKA at our institution from May 2020 to July 2022 were identified. Patient demographics, surgical time, length of stay and 30-day readmission, revision surgery, and complication rates were prospectively collected. Preoperative and postoperative Hip and Knee Society (Hip Osteoarthritis Outcome Score [HOOS] and Knee Osteoarthritis Outcome Score [KOOS]) were collected. Patients were stratified by BMI as ideal weight (20 to 24.9), overweight (25 to 29.9), class I obese (30 to 34.9), class II obese (35 to 39.9), and morbidly obese (>40 m/kg2). A total of 1,423 patients were included for final analysis. No difference was observed in 30-day unplanned return to emergency department, readmission, or revision surgery in the morbidly obese cohort. Morbidly obese patients undergoing THA had lower preoperative HOOS (49.5 versus 54.5, P = 0.004); however, there was no difference in postoperative HOOS or KOOS at 12 months across all cohorts. No difference was observed in 30-day return to emergency department, readmission, or revision surgery in the morbidly obese cohort. Despite a lower preoperative HOOS, there was no difference in 12-month HOOS or KOOS when stratified by BMI. These findings suggest that such patients may achieve similar benefit from arthroplasty as their ideal weight counterparts.

Impact of exercise training on endothelial metabolism and skeletal muscle angiogenic potential in type 2 diabetes

Type 2 diabetes (T2D) is associated with vascular endothelial dysfunction and microvascular rarefaction in skeletal muscle tissue (1). Although endothelial dysfunction in metabolic disease is proposed to be associated with altered endothelial cell metabolism, there is to date a paucity of human data to support this notion. The aim of this study was to investigate the metabolism in microvascular endothelial cells derived from skeletal muscle biopsies. Moreover, as exercise training is known to reverse endothelial dysfunction and promote angiogenesis, the effect of a period of exercise training was assessed. Microvascular endothelial cells were isolated from m. vastus lateralis biopsies taken from obese individuals with (n = 7) and without (n = 8) T2D before and after 12 weeks of aerobic exercise training. Mitochondrial respiration, hydrogen peroxide (H2O2) emission, and nitric oxide (NO) formation were determined in the cells by the Oroboros Oxygraph-2K. In addition, angiogenic-, metabolic- and antioxidant enzymes and proteins, cell proliferation, and skeletal muscle capillarization were determined. At baseline, there was no difference between endothelial cells from obese control participants and T2D obese participants for any of the parameters measured: glycolytic capacity, as evidenced by a similar lactate production and PFK-1 protein content, respiratory capacity, H2O2 emission, NO emission, endothelial NO synthase protein (eNOS) content. The training period led to an overall increase in the respiratory capacity in endothelial cells from both groups (main effect, P = 0.021) whereas mitochondrial H2O2 emission remained unaltered. There was no change in glycolytic capacity, superoxide dismutase 2 or eNOS protein contents, or NO emission. Training did not influence the capillary-to-muscle fiber ratio in either group. The results of this study show that aerobic exercise training of obese control and obese diabetic subjects leads to an increase in the respiratory capacity of muscle microvascular endothelial cells. The data also indicate that there are no differences in endothelial metabolism and NO production between obese control and obese diabetic individuals. However, as the study is ongoing and only half of the subjects have been included at this time, power is limited and results may differ upon completion. Data from all subjects will be presented at the conference. Funding: The study is funded by Novo Nordisk A/S. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Associations between GRM7 polymorphisms and obesity in patients selected for sleeve gastrectomy.

Obesity is a worldwide problem in which genetic factors have a prominent role. We have selected two single nucleotide polymorphisms (SNPs) within glutamate metabotropic receptor 7 (GRM7) gene, namely rs6782011 and rs779867 to weigh their association with obesity in an Iranian cohort. The distribution of rs6782011 alleles was significantly different in the obese patients from normal controls (P < 0.0001; 434 obese patients vs. 297 normal controls). Distribution of alleles was also measured between sex-based groups of obese patients and controls. We detected remarkable differences between female obese cases and female control subjects (P < 0.0001; 374 female obese cases vs. 216 female normal controls); nevertheless, the difference in allele distribution was not significant for male cases compared with corresponding normal controls (p = 0.47; 60 male patients vs. 81 normal males). Contrariwise, distribution of rs779867 alleles was not significantly different between total obese patients compared with normal controls (P = 0.21; 434 obese patients vs. 297 normal BMI controls). There was also no significant difference for female and male obese patients compared with female and male normal BMI controls. Thus, GRM7 can be considered as a risk locus for obesity.

Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation, fluid sheer stress, and inflammatory pathways in obesity-related glomerulopathy

Obesity-related glomerulopathy (ORG) is an independent risk factor for chronic kidney disease and even progression to end-stage renal disease. Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG, but relatively little is known about cell-specific changes in gene expression. To define the transcriptomic landscape at single-cell resolution, we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing. We report for the first time that immune cells, including T cells and B cells, are decreased in ORG patients. Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells. This gene is related to inflammation and cell proliferation. Analysis of differential gene expression in glomerular cells (endothelial cells, mesangial cells, and podocytes) showed that these cell types were mainly enriched in genes related to oxidative phosphorylation, cell adhesion, thermogenesis, and inflammatory pathways (PI3K-Akt signaling, MAPK signaling). Furthermore, we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway. Moreover, an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients, with major interactions between parietal epithelial cells and podocytes. Altogether, our identification of molecular events, cell types, and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

Transferrin receptor levels and its rare variant are associated with human obesity.

Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown. To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon-sequencing and genetic assessments were conducted of a case-control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole-exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis. TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild-type. Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.

Altered gut microbiota of obesity subjects promotes colorectal carcinogenesis in mice.

Obesity is a risk factor for colorectal cancer (CRC). The role of gut microbiota in mediating the cancer-promoting effect of obesity is unknown. Azoxymethane (AOM)-treated, ApcMin/+ and germ-free mice were gavaged with feces from obese individuals and control subjects respectively. The colonic tumor load and number were recorded at the endpoint in two carcinogenic models. The gut microbiota composition and colonic transcriptome were assessed by metagenomic sequencing and RNA sequencing, respectively. The anticancer effects of bacteria depleted in fecal samples of obese individuals were validated. Conventional AOM-treated and ApcMin/+ mice receiving feces from obese individuals showed significantly increased colon tumor formation compared with those receiving feces from control subjects. AOM-treated mice receiving feces from obese individuals showed impaired intestinal barrier function and significant upregulation of pro-inflammatory cytokines and activation of oncogenic Wnt signaling pathway. Consistently, transferring feces from obese individuals to germ-free mice led to increased colonic cell proliferation, intestinal barrier function impairment, and induction of oncogenic and proinflammatory gene expression. Moreover, germ-free mice transplanted with feces from obese human donors had increased abundance of potential pathobiont Alistipes finegoldii, and reduced abundance of commensals Bacteroides vulgatus and Akkermansia muciniphila compared with those receiving feces from human donors with normal body mass index (BMI). Validation experiments showed that B.vulgatus and A.muciniphila demonstrated anti-proliferative effects in CRC, while A.finegoldii promoted CRC tumor growth. Our results supported the role of obesity-associated microbiota in colorectal carcinogenesis and identified putative bacterial candidates that may mediate its mechanisms. Microbiota modulation in obese individuals may provide new approaches to prevent or treat obesity-related cancers including CRC. This work was funded by National Key Research and Development Program of China (2020YFA0509200/2020YFA0509203), National Natural Science Foundation of China (81922082), RGC Theme-based Research Scheme Hong Kong (T21-705/20-N), RGC Research Impact Fund Hong Kong (R4632-21F), RGC-CRF Hong Kong (C4039-19GF and C7065-18GF), RGC-GRF Hong Kong (14110819, 14111621), and NTU Start-Up Grant (021337-00001).

A Longitudinal Study in Turkiye of Host Ability to Produce Antibodies following a Third Homologous BNT162b2 Vaccination.

Obesity is a multifaceted, complex condition that has negative impacts on one's health. There are conflicting reports regarding the COVID-19 vaccine's ability to induce antibody formation in obese people. Our study aimed to determine anti-S-RBD IgG and surrogate neutralizing antibody (snAb) levels before and after the third Pfizer-BioNTech (BNT162b2) vaccination (at 15, 60, 90, and 120 days) in normal-weight adults, overweight, and obese individuals without any comorbidity or previous SARS-CoV-2 infection history, but it did not evaluate the response to the first two doses. In this longitudinal prospective study in Istanbul, Turkey, a total of 323 consecutive adult individuals (141 normal weight, 108 overweight, and 74 patients with obesity) were included. Peripheral blood samples were collected. Anti-S-RBD IgG and surrogate neutralizing antibody levels were detected using the ELISA method. After the third dose of BNT162b2 vaccination, obese patients had significantly lower levels of snAb against SARS-CoV-2 compared with normal-weight controls, but the levels otherwise did not differ between the study groups. Across all individuals in our cohort, titers peaked about a month after this third vaccination and then gradually faded. Anti-S-RBD IgG and snAb IH% levels against SARS-CoV-2 were not correlated with IL-6 and TNF-α levels. In conclusion, anti-S-RBD IgG titers and snAb IH% levels against SARS-CoV-2 were determined longitudinally for 120 days after the third homologous BNT162b2 vaccination. Although there were no significant differences in anti-S-RBD IgG, we found significant differences in the snAb IH% levels against SARS-CoV-2 between obese and healthy control subjects.

Peripheral Airway Dysfunction in Obesity and Obese Asthma

The purpose of this study was to investigate physiological phenotypes of asthma in obesity. Do physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity? Cross-sectional study of people with obesity (31 with asthma and 22 without lung disease). Participants underwent methacholine challenge testing with measurement of spirometry and respiratory system impedance by oscillometry. Participants had class III obesity (BMI, 46.7 ± 6.6kg/m2 in control subjects and 47.2 ± 8.2kg/m2 in people with asthma). Most participants had significant changes in peripheral airway impedance in response to methacholine: in control subjects, resistance at 5Hz measured by oscillometry increased by 45%± 27%and area under the reactance curve (AX) by 268%± 236%in response to 16mg/mL methacholine; in people with asthma, resistance at 5Hz measured by oscillometry increased by 52%± 38%and AX by 361%± 295%in response to provocation concentration producing a 20% fall in FEV1 dose of methacholine. These responses suggest that obesity predisposes to peripheral airway reactivity. Two distinct groups of asthma emerged based on respiratory system impedance: one with lower reactance (baseline AX, 11.8; interquartile range, 9.9-23.4cm H2O/L) and more concordant bronchoconstriction in central and peripheral airways; the other with high reactance (baseline AX, 46.7; interquartile range, 23.2-53.7cm H2O/L) and discordant bronchoconstriction responses in central and peripheral airways. The high reactance asthma group included only women, and reported significantly more gastroesophageal reflux disease, worse chest tightness, more wheeze, and more asthma exacerbations than the low reactance group. Peripheral airway reactivity detected by oscillometry is common in obese control subjects and obese people with asthma. There is a subgroup of obese asthma characterized by significant peripheral airway dysfunction by oscillometry out of proportion to spirometric airway dysfunction. This peripheral dysfunction represents clinically significant respiratory disease not readily assessed by spirometry.

The role of the platelet pool of Plasminogen Activator Inhibitor-1 in well-controlled type 2 diabetes patients.

BackgroundThe main inhibitor of the fibrinolytic system, Plasminogen Activator Inhibitor -1 (PAI-1), irreversibly binds tissue-type Plasminogen Activator (t-PA) and thereby inhibits the protective action of tPA against thrombus formation. Elevated levels of plasma PAI-1 are associated with an increased risk of cardiovascular events and are observed in subjects with type 2 diabetes (T2D) and obesity. Platelets contain the majority of PAI-1 present in blood and exhibit the ability to synthesis active PAI-1. Diabetic platelets are known to be hyper-reactive and larger in size; however, whether these features affect their contribution to the elevated levels of plasma PAI-1 in T2D is not established.ObjectivesTo characterize the PAI-1 antigen content and the mRNA expression in platelets from T2D subjects compared to obese and lean control subjects, in order to elucidate the role of platelet PAI-1 in T2D.MethodsNine subjects with T2D and obesity were recruited from Primary Care Centers together with 15 healthy control subjects (8 lean subjects and 7 with obesity). PAI-1 antigen levels in plasma, serum and platelets were determined by ELISA, and PAI-1 mRNA expression was analyzed by qPCR.ResultsThere was no significant difference in PAI-1 mRNA expression or PAI-1 antigen in platelets in T2D subject in comparison to obese and lean control subjects. An elevated level of plasma PAI-1 was seen in both T2D and obese subjects. PAI-1 gene expression was significantly higher in both obese groups compared to lean.ConclusionSimilar levels of protein and mRNA expression of PAI-1 in platelets from T2D, obese and lean subjects indicate a limited role of platelets for the elevated plasma PAI-1 levels. However, an increased synthesis rate of mRNA transcripts in platelets from T2D and an increased release of PAI-1 could also result in similar mRNA and protein levels. Hence, synthesis and release rates of PAI-1 from platelets in T2D and obesity need to be investigated to further elucidate the role of platelets in obesity and T2D.

Obese Skeletal Muscle-Expressed Interferon Regulatory Factor 4 Transcriptionally Regulates Mitochondrial Branched-Chain Aminotransferase Reprogramming Metabolome.

In addition to the significant role in physical activity, skeletal muscle also contributes to health through the storage and use of macronutrients associated with energy homeostasis. However, the mechanisms of regulating integrated metabolism in skeletal muscle are not well-defined. Here, we compared the skeletal muscle transcriptome from obese and lean control subjects in different species (human and mouse) and found that interferon regulatory factor 4 (IRF4), an inflammation-immune transcription factor, conservatively increased in obese subjects. Thus, we investigated whether IRF4 gain of function in the skeletal muscle predisposed to obesity and insulin resistance. Conversely, mice with specific IRF4 loss in skeletal muscle showed protection against the metabolic effects of high-fat diet, increased branched-chain amino acids (BCAA) level of serum and muscle, and reprogrammed metabolome in serum. Mechanistically, IRF4 could transcriptionally upregulate mitochondrial branched-chain aminotransferase (BCATm) expression; subsequently, the enhanced BCATm could counteract the effects caused by IRF4 deletion. Furthermore, we demonstrated that IRF4 ablation in skeletal muscle enhanced mitochondrial activity, BCAA, and fatty acid oxidation in a BCATm-dependent manner. Taken together, these studies, for the first time, established IRF4 as a novel metabolic driver of macronutrients via BCATm in skeletal muscle in terms of diet-induced obesity.

Oral motor function in obesity.

Obese individuals may have impaired oral sensory functioning and abnormal oral motor function, a consequence of fat deposition in muscles. To evaluate the oral motor function in obese individuals. Three observational cross-sectional studies were performed. In total, 140 participants were evaluated: (1) orofacial myofunctional evaluation (OMES) was performed in 26 obese and 26 control subjects; (2) time taken for suction of 50ml of water through straws of 3mm and 6mm of diameter was measured in 30 obese and 30 control subjects; (3) the oral phase of swallowing of 5ml moderately thick and 5ml extremely thick boluses was analysed by videofluoroscopy in 14 obese and 14 control subjects. Obese and non-obese control subjects had body mass index ≥40kg/m2 and <30kg/m2 , respectively. Obese subjects had worse oral myofunctional evaluation scores in posture/appearance (lips, jaw, cheeks, tongue and hard palate), in mobility (lips, tongue, jaw and cheeks) and in breathing, deglutition and mastication functions (p≤.020). The OMES total score was 73.5±5.5 in obese and 92.8±3.7 in controls subjects (p<.001). There was no difference between the groups in the time taken for 50ml of water suction through the 3-mm- or 6-mm-diameter straw. Videofluoroscopic evaluation of the bolus swallowed demonstrated a longer oral preparation time in obese individuals for both boluses (p≤.040) and no difference in oral transit time (p≥.140). A moderate change in oral motor function was observed in obese individuals with BMI ≥40kg/m2 .

Association of chemokines IP-10/CXCL10 and I-TAC/CXCL11 with insulin resistance and enhance leukocyte endothelial arrest in obesity.

Obesity is a key contributing factor to incidental type 2 diabetes and cardiovascular disease. CXCR3 receptor and its ligands CXCL 10 and 11 are associated with atherosclerosis and cardiovascular disease. The aim of our study was to analyse the role of the CXCR3 ligands on insulin resistance (IR) and endothelial dysfunction in human obesity. We have studied 45 obese patients (mean age 44±6years, body mass index 45±9kg/m2) who were selected for Roux-Y-gastric bypass surgery and 21 non obese control subjects with similar age and gender distribution. We measured by ELISA the circulating levels of the CXCR3 ligands interferon-γ inducible protein 10 (IP-10/CXCL10) and interferon-γ-inducible T-cell alpha chemoattractant (I-TAC/CXCL11). Using an ex vivo procedure with the flow chamber assay, we have investigated the effect of such chemokines on endothelial leukocytes arrest under dynamic conditions. Peripheral blood levels of CXCL10 and CXCL11 were significantly higher in obese subjects than in controls (p<0.001) and significantly correlated with BMI, waist circunference and HOMA-IR. Obese patients with HOMA-IR index above 75th percentile showed highest increase of circulating CXCL10 and CXCL11 values. Under dynamic flow conditions, the enhanced adhesion of patient leukocytes to TNFα-induced human arterial endothelial cells was partly dependent on CXCR3. The study demonstrates that CXCL10 and CXCL11 are associated with IR and enhance leukocyte endothelial arrest in obese subjects. Blockade of CXCR3 signaling might be a new therapeutic approach for the prevention of obesity-associated cardiovascular co-morbidities.

Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin.

Bariatric surgery is an effective treatment for severe obesity and related comorbidities, such as type II diabetes. Gastric bypass surgery shortens the length of the intestine, possibly leading to altered drug absorption. Metformin, a first-line treatment for type II diabetes, has permeability-dependent drug absorption, which may be sensitive to intestinal anatomic changes during bypass surgery, including Roux-en-Y gastric bypass (RYGB). Previous computer simulation data indicate increased metformin absorption after RYGB. In this study, we experimentally determined the region-dependent permeability of metformin, using the rat single-pass intestinal perfusion method (SPIP), which we then implemented into GastroPlusTM to assess the contribution of our SPIP data to post-RYGB metformin absorption modeling. Previous simulations allowed a good fit with in vivo literature data on healthy and obese control subjects. However, it was revealed that for post-RYGB drug absorption predictions, simply excluding the duodenum/jejunum is insufficient, as the software underestimates the observed plasma concentrations post-RYGB. By implementing experimentally determined segmental-dependent permeabilities for metformin in the remaining segments post-surgery, GastroPlusTM proved to fit the observed plasma concentration profile, making it a useful tool for predicting drug absorption after gastric bypass. Reliable evaluation of the parameters dictating drug absorption is required for the accurate prediction of overall absorption after bariatric surgery.

Gas chromatography/mass spectrometry analysis of organic acid profiles in human serum: A protocol of direct ultrasound-assisted derivatization.

Low-molecular-weight organic acids that generally contain one to three carboxyl groups are involved in many important biological processes; therefore, it is important to develop a quantitative method for analyzing organic acids in serum in order to allow an evaluation of metabolic changes. In this study, we evaluated a protocol for detecting 26 organic acids in serum based on ultrasound-assisted derivatization by gas chromatography/mass spectrometry (GC/MS). Serum samples were prepared using ultrasound-assisted silane derivatization before GC/MS analysis to quantify concentrations of organic acids. Additionally, we investigated the variables affecting derivatization yields, including the extraction solvent, derivatization reagents, and derivatization conditions (reaction temperature, duration, and sonication parameters). The protocol was ultimately applied to detect organic acid profiles related to obesity. We used acetone as the extraction solvent and determined suitable derivatization conditions, as follows: BSTFA + 1% TMCS, 50°C, 10min, and 100% ultrasound power. The protocol showed satisfactory linearity (r = 0.9958-0.9996), a low limit of detection (0.04-0.42 μmol/L), good reproducibility (coefficient of variation (CV) %: 0.32-13.76%), acceptable accuracy (recovery: 82.97-114.96%), and good stability within 5days (CV%: 1.35-12.01% at room temperature, 1.24-14.09% at 4°C, and 1.01-11.67% at -20°C). Moreover, the protocol was successfully applied to obtain the organic acid profiles from obese and healthy control subjects. We identified and validated a protocol for ultrasound-assisted derivatization prior to GC/MS analysis for detecting 26 kinds of organic acids in serum. The results suggest the efficacy of this protocol for clinical applications to determine metabolic changes related to fluctuations in organic acid profiles.

Effect of Obesity on Tissue Factor, Tissue Plasminogen Activator and Plasminogen Activator Inhibitor Among Obese People in Sapele Southern Nigeria

<i>Background/Objective</i>: Obesity is a medical condition in which adipose tissue accumulates to the extent of having adverse effect on certain procaogulant factors such as: Human Plasminogen Activator Inhibitor (PAI), tissue Plasminogen Activator (t-PA) and Tissue Factor (TF) of adults in Nigeria. This study therefore aims to evaluate the impacts of obesity on PAI, t-PA, and TF in obese adult in Sapele, South-South Nigeria. <i>Materials and Methods</i>: 312 adults with obesity and 103 normal adults (used as controls) with age between 18 and 65 years were enrolled for this study. 4.5mls of venous blood was collected into EDTA containers for procoagulant activity measurement. Human Plasminogen Activator Inhibitor (PAI-1), Human tissue Plasminogen Activator (t-PA), and Human Tissue Factor (TF) values were determined using Enzyme Linked Immunosorbent Assay (ELISA) methods. Collated data was analyzed using Student’s t-test, correlation and one-way ANOVA followed by LSD post-hoc test and results were expressed as mean±standard deviation. <i>Results</i>: The BMI (Body Mass Index) of obese subjects and control subjects were 36.82±0.55kg/m² and 20.43±0.29 kg/m² respectively at p<0.001. t-PA level of obese subject was 344.34±43.58pg/ml while control group had t-PA value of 192.46±10.65pg/ml. In addition, PAI of obese people was 367.24±27.49pg/ml and control subject had PAI value of 253.37±11.11pg/ml. Human Tissue Factor (TF) of obese subject and control subjects were 93.31±7.25pg/ml and 66.59±2.76pg/ml respectively at p<0.01. <i>Conclusion</i>: The values of Plasminogen Activator Inhibitor, tissue Plasminogen Activator, and Human Tissue Factor were higher in people with obesity when compare with non-obese control group in Sapele Southern Nigeria.

Duodenal Metatranscriptomics to Define Human and Microbial Functional Alterations Associated with Severe Obesity: A Pilot Study.

Obesity is a multifactorial disorder, and the gut microbiome has been suggested to contribute to its onset. In order to better clarify the role of the microbiome in obesity, we evaluated the metatranscriptome in duodenal biopsies from a cohort of 23 adult severely obese and lean control subjects using next generation sequencing. Our aim was to provide a general picture of the duodenal metatranscriptome associated with severe obesity. We found altered expressions of human and microbial genes in the obese compared to lean subjects, with most of the gene alterations being present in the carbohydrate, protein, and lipid metabolic pathways. Defects were also present in several human genes involved in epithelial intestinal cells differentiation and function, as well as in the immunity/inflammation pathways. Moreover, the microbial taxa abundance inferred by our transcriptomic data differed in part from the data that we previously evaluated by 16S rRNA in 13/23 individuals of our cohort, particularly concerning the Firmicutes and Proteobacteria phyla abundances. In conclusion, our pilot study provides the first taxonomic and functional characterization of duodenal microbiota in severely obese subjects and lean controls. Our findings suggest that duodenal microbiome and human genes both play a role in deregulating metabolic pathways, likely affecting energy metabolism and thus contributing to the obese phenotype.

Evaluation of cyclooxygenase oxylipins as potential biomarker for obesity-associated adipose tissue inflammation and type 2 diabetes using targeted multiple reaction monitoring mass spectrometry

Introduction: Obesity is associated with adipose tissue inflammation which in turn drives insulin resistance and the development of type 2 diabetes. Oxylipins are a collection of lipid metabolites, subdivided in different classes, which are involved in inflammatory cascades. They play important roles in regulating adipose tissue homeostasis and inflammation and are therefore putative biomarkers for obesity-associated adipose tissue inflammation and the subsequent risk of type 2 diabetes onset. The objective for this study is to design an assay for a specific oxylipin class and evaluate these as potential prognostic biomarker for obesity-associated adipose tissue inflammation and type 2 diabetes. Methods: An optimized workflow was developed to extract oxylipins from plasma using solid-phase extraction followed by analysis using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer in multiple reaction monitoring mode. This workflow was applied to clinical plasma samples obtained from obese-type 2 diabetes patients and from lean and obese control subjects. Results: The assay was analytically validated and enabled reproducible analyses of oxylipins extracted from plasma with acceptable sensitivities. Analysis of clinical samples revealed discriminative values for four oxylipins between the type 2 diabetes patients and the lean and obese control subjects, viz. PGF2α, PGE2, 15-keto-PGE2 and 13,14-dihydro-15-keto-PGE2. The combination of PGF2α and 15-keto-PGE2 had the most predictive value to discriminate type 2 diabetic patients from lean and obese controls. Conclusions: This proof-of-principle study demonstrates the potential value of oxylipins as biomarkers to discriminate obese individuals from obese-type 2 diabetes patients.

Diagnostic value of salivary cortisol in 1-mg dexamethasone suppression test

BACKGROUND: Late-night salivary cortisol and serum cortisol measurements after 1-mg Dexamethasone Suppression Test (1-mg DST) are routinely used to diagnose Cushings syndrome (CS). Measuring morning salivary instead of serum cortisol after 1-mg DST would make the diagnostics of CS fully non-invasive.&#x0D; AIM: To evaluate the diagnostic accuracy of salivary cortisol in 1-mg DST as measured by electrochemiluminescence assay (ECLIA).&#x0D; MATERIALS AND METHODS: We combined a cohort diagnostic study, including 164 participants (132 females, 32 males) aged from 18 to 77 years: 110 were overweight or obese as increased BMI is the most common sign of Cushings Syndrome (CS), and 54 healthy volunteers. In each cohort late-night salivary cortisol was measured (at 23:00) followed by 1-mg DST and blood and salivary sampling for cortisol measurement the next morning at 08:00-09:00. Cortisol in saliva and serum were measured on automatic analyzer Cobas е 601 by F. Hoffmann-La Roche Ltd, using ECLIA. The final diagnosis was confirmed by the histological evaluation after surgery or using a follow-up observation in patients with obesity to exclude Cushings syndrome manifestation.&#x0D; RESULTS: Among 110 patients, 54 subjects were finally confirmed as having Cushing's syndrome. Reference interval for salivary cortisol after 1-mg DST was estimated to be 0,512,7 nmol/l (595 procentile). Maximal salivary cortisol level in 1-mg DST registered in healthy person was 29,6 mmol/l. Areas under the curve (AUC) were as following: for salivary cortisol in 1-mg DST 0,838 (95% СI 0,7720,905), for blood cortisol in 1-mg DST 0,965 (95% CI 0,9390,992) and for late-night salivary cortisol 0,925 (95% CI 0,8820,969). The optimal cut-off point for salivary cortisol after 1-mg DST was estimated as 12.1 nmol/l (sensitivity 60%, specificity 92,9%) among CS versus healthy subjects; 12,6 (sensitivity 58,2%, specificity 96,2%) among patients with obesity and CS; and 12,2 nmol/l (sensitivity 60,7%, specificity 93,4%) among CS and both obese and healthy control subjects. Considering small difference between cut-off points, the recommended cut-off value for salivary cortisol after 1-mg DST is recommended to be 12,0 nmol/l if measured by ECLIA.&#x0D; CONCLUSION: Although salivary cortisol after 1-mg DST is inferior to serum cortisol after 1-mg DST in the diagnostic performance and diagnostic accuracy, it can be used as a low-invasive screening test with superior specificity.

Increased Oxidative Stress, Altered Trace Elements, and Macro-Minerals Are Associated with Female Obesity.

Generally female individuals are more prone to obesity due to their lifestyle and physiology. However, female individuals have got little attention in this aspect. This pioneering study designed to find the level of serum malondialdehyde (MDA), non-enzymatic antioxidant (vitamin C), other trace elements (zinc and iron), and macro-minerals (sodium, potassium, and calcium) for female obesity determining its role and action in disease diagnosis along with propagation. For this prospective case-control study, 70 female obese and 70 healthy individuals were evaluated. Serum lipid peroxidation product malondialdehyde (MDA) concentration was measured to determine the level of lipid peroxidation. UV spectrophotometric method was implemented for vitamin C concentration to measure serum ascorbic acid. Atomic absorption spectroscopy (AAS) was implemented to determine serum macro-minerals (Na, K, and Ca), and trace elements (Zn and Fe) were estimated. For statistical analysis, student's t-test and Pearson's correlation test were executed. A significantly higher concentration of serum MDA (p < 0.001) and low concentration of antioxidants (vitamin C) (p < 0.001) are observed in patient than control group. We found a lower concentration of trace elements (zinc, iron) and macro-minerals (sodium, potassium, and calcium) in patients compared to control except sodium. The mean concentrations for serum Zn, Fe, Na, K, and Ca were 0.34 ± 0.01, 0.25 ± 0.01, 3828.91 ± 205.09, 90.42 ± 6.45, and 43.04 ± 2.38mg/L and 0.78 ± 0.08, 0.84 ± 0.08, 2600.97 ± 99.79, 223.79 ± 14.64, and 86.43 ± 2.78mg/L, respectively, for female obese patients and control subjects (p < 0.001). We can suggest from our study that there is a strong association of female obesity with increased serum concentrations of MDA and reduced non-enzymatic antioxidant vitamin C and different serum trace metals and macro-minerals.

Profiling the Oral Microbiome and Plasma Biochemistry of Obese Hyperglycemic Subjects in Qatar.

The present study is designed to compare demographic characteristics, plasma biochemistry, and the oral microbiome in obese (N = 37) and lean control (N = 36) subjects enrolled at Qatar Biobank, Qatar. Plasma hormones, enzymes, and lipid profiles were analyzed at Hamad Medical Cooperation Diagnostic Laboratory. Saliva microbiome characterization was carried out by 16S rRNA amplicon sequencing using Illumina MiSeq platform. Obese subjects had higher testosterone and sex hormone-binding globulin (SHBG) concentrations compared to the control group. A negative association between BMI and testosterone (p < 0.001, r = −0.64) and SHBG (p < 0.001, r = −0.34) was observed. Irrespective of the study groups, the oral microbiome was predominantly occupied by Streptococcus, Prevotella, and Veillonella species. A generalized linear model revealed that the Firmicutes/Bacteroidetes ratio (2.25 ± 1.83 vs. 1.76 ± 0.58; corrected p-value = 0.04) was higher, and phylum Fusobacteria concentration (4.5 ± 3.0 vs. 6.2 ± 4.3; corrected p-value = 0.05) was low in the obese group compared with the control group. However, no differences in microbiome diversity were observed between the two groups as evaluated by alpha (Kruskal–Wallis p ≥ 0.78) and beta (PERMANOVA p = 0.37) diversity indexes. Certain bacterial phyla (Acidobacteria, Bacteroidetes, Fusobacteria, Proteobacteria, Spirochaetes, and Firmicutes/Bacteroidetes) were positively associated (p = 0.05, r ≤ +0.5) with estradiol, fast food consumption, creatinine, breastfed during infancy, triglycerides, and thyroid-stimulating hormone concentrations. In conclusion, no differences in oral microbiome diversity were observed between the studied groups. However, the Firmicutes/Bacteroidetes ratio, a recognized obesogenic microbiome trait, was higher in the obese subjects. Further studies are warranted to confirm these findings in a larger cohort.