OB Group Research Articles

Serum adropin is unaltered in adolescents with histology-confirmed steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) in adolescents is increasing. Adropin is a liver-derived peptide involved in glucose and lipid homeostasis that was shown to be reduced in adults with metabolic disorders and cardiovascular disease (CVD). Serum adropin may also be higher in young men than women. A prior study reported that serum adropin was reduced in adolescents with MASLD, but the relationship between liver histology and CVD risk factors was not reported. We tested the hypotheses that adropin is (1) reduced in adolescents with MASLD compared to adolescents with obesity (Ob) or normal weight (NW) without MASLD, (2) correlated with blood pressure, arterial stiffness, and liver histopathology, and (3) higher in boys than girls. Serum adropin was measured in 47 patients with MASLD, and 27 and 29 control participants with Ob or NW, respectively. Adropin was not reduced but was instead 5% and 20% higher (p > 0.42) in the MASLD compared to the Ob and NW groups, respectively. Adropin concentration was not correlated with arterial stiffness or blood pressure. Adropin was 20% higher in boys than girls in the entire study cohort (p = 0.034). This difference was evident in the Ob group (p = 0.018), but not in the NW (p = 0.537) or the MASLD (p = 0.893) groups. Adropin was positively correlated with age within the MASLD group only (r = 0.46, p < 0.001). Serum adropin was not reduced in adolescents with Ob or MASLD as reported previously. The positive relationship between age and adropin in adolescents with MASLD requires further examination.

Obesity cardiomyopathy could contribute to sudden cardiac death: a Japanese epidemiological morphological study

BackgroundWe aimed to clarify the existence and pathological features of obesity cardiomyopathy (OCM) in Japan using our series of autopsy cases.MethodsIn this retrospective autopsy study, OCM was defined as cardiac hypertrophy (≥ 400 g in men, ≥ 320 g in women) of unknown aetiology in individuals with obesity (body mass index [BMI] ≥ 25 kg/m2 according to the Japanese definition of obesity). We compared cases of OCM with those with obesity without cardiac hypertrophy (OB) and normal weight without cardiac hypertrophy (normal control). Macroscopically, heart weight and cardiac parameters, including epicardial adipose tissue, were measured. Fibrosis, cardiomyocyte diameter, and adipose tissue infiltration were analysed microscopically.ResultsOf the 294 cases, we identified 19 cases of OCM (6.5%) and compared them with the OB and normal control groups. Patients with OCM were slightly younger than non-OCM patients (p = 0.081). The median heart weight was significantly heavier in OCM cases than in OB cases (435 g, interquartile range [IQR] 408–515 g vs. 360 g, IQR 341–385 g). Macroscopically, OCM hearts had a “globoid” appearance with a thickened right ventricular outflow tract. Some OCM cases showed focal interstitial fibrosis in the left ventricle. Approximately half the OCM cases were diagnosed with sudden cardiac death (SCD), with significant differences.ConclusionsThe prevalence of OCM may be higher than expected in Japan, and this may be a specific pathological finding. Given that approximately half the cases of OCM were due to SCD, OCM may cause SCD, emphasizing the need to recognise and diagnose OCM.

The decorin and myostatin response to acute whole body vibration: impact of adiposity, sex, and race

BackgroundTraditional forms of exercise affect immune, metabolic, and myokine responses and contribute to a multitude of health benefits. Whole body vibration (WBV) has recently emerged as an exercise mimetic that may be more tolerable for those individuals that cannot perform traditional exercise. However, the myokines response to acute WBV in humans has yet to be fully elucidated.ObjectiveTo characterize the decorin and myostatin response to acute whole body vibration (WBV) and determine the impact of adiposity, sex, and race.SubjectsOne hundred twenty-nine adults (32.8 ± 0.4 years, 66.7% female, 53.5% non-Hispanic Black) were recruited as part of an ongoing, longitudinal twin cohort parent study. Participants were classified into three groups: those with obesity (OB: ≥30 kg/m2), those who are overweight (OW: ≥25 and <30 kg/m2), or those with normal weight (NW: <25 kg/m2) based on BMI.MethodsBlood was collected at baseline (PRE), immediately post (POST), and 1 h (1H), 3 h (3H), and 24 h (24H) post WBV. The acute WBV protocol consisted of 10 cycles of 1 min of vibration exercise followed by 30 s of standing rest.ResultsThe response was similar between NW and OW, so these groups were combined for analysis (NW/OW: BMI < 30 kg/m2). Overall, circulating concentrations of decorin were higher (p < 0.001) POST (8.80 ± 0.19 pg/mL) and significantly lower (p’s ≤ 0.005) at 1H (8.66 ± 0.19 pg/mL) and 3H (8.68 ± 0.19 pg/mL), compared to PRE (8.71 ± 0.19 pg/mL). Decorin POST was greater (p = 0.016) in the OB group (8.82 ± 0.18 pg/mL) compared to the NW/OW group (8.77 ± 0.20 pg/mL). Overall, myostatin was higher (p = 0.002) POST (54.93 ± 1.04 pg/mL) and lower (p < 0.001) at 24H (49.13 ± 1.04 pg/mL) compared to PRE (53.49 ± 1.04 pg/mL). The myostatin response was lower (p’s ≤ 0.001) in female and non-Hispanic White individuals compared to male and non-Hispanic Black individuals, respectively.ConclusionsA single bout of WBV can facilitate the release of decorin and myostatin into circulation, a similar response to traditional exercise. Additionally, adiposity, sex and race should be considered when evaluating the myokines response to WBV.

Whole tomato lipidic extract improved sperm quality in obese rats induced by a high-carbohydrate diet.

Obesity represents a risk in the development of metabolic and oxidative stress (OS), as well as in male infertility. There is still no pharmacological treatment for obesity-induced male infertility, but the use of natural antioxidants has been proposed as a treatment. The aim of this work is to evaluate the effect of a whole tomato lipid extract on rats that decreased their fertility and spermatogenesis after being induced obese with a high carbohydrate diet. One hundred fourteen male Wistar rats of 12weeks of age were used. Two groups were randomly formed non-obese control group (C, n=54) and obese group (Ob, n=54) that received 30% w/v sucrose solution for 3 months. Subsequently, the C and Ob group were divided into two groups: vehicle (C-Vh and Ob-Vh) that received corn oil as vehicle and tomato lipid extract (C-Ex and Ob-Ex) that received whole tomato lipid extract. The groups that received a hypercaloric diet had a gain in visceral and retroperitoneal adipose tissue, an increase in total cholesterol and triglyceride levels, increased OS in the testis, and lesions in testicular histology, as well as a reduction in testicular size and sperm quality parameters (motility, viability, and concentration). Treatment with whole tomato lipid extract significantly decreased the weight of gonadal adipose tissue and OS, maintained testicular size, showed a significant increase in sperm quality parameters and improved histology of seminiferous tubules. These results demonstrate a greater therapeutic and beneficial effect of the tomato lipid extract on sperm quality parameters in obese rats and therefore on fertility.

Treatment Strategies and Long-Term Outcomes in Silent Corticotroph Adenomas: A Single-Center Retrospective Study of 367 Cases.

Silent corticotroph adenoma (SCA) is a high-risk pituitary neuroendocrine tumor (PitNET) which exhibits more aggressive behavior than other nonfunctioning PitNETs. Some SCAs are observed to recur after total resection (TR). We aim to discuss the long-term outcomes after endoscopic endonasal surgery for SCAs and explore optimal treatment after operation. Clinical data and intraoperative videos from 367 SCAs who underwent endoscopic endonasal surgery were retrospectively collected. Patients were categorized into TR and subtotal resection (STR) groups according to 3-month postoperative MRIs. Based on close-up intraoperative observation of the relationship between tumor and pituitary gland, diaphragm, and medial wall cavernous sinus, patients in the TR group were further subdivided into gross total resection (GTR) and near total resection (NTR) groups. Patients in the STR group were subdivided as STR followed by observation (STR + ob) and STR followed by adjuvant stereotactic radiosurgery (SRS) (STR + SRS). Kaplan-Meier analysis was used to compare the event-free survival among these subgroups. Headache (27.5%) and vision loss (55.3%) were the most common presenting symptoms. Cavernous sinus (CS) invasion was confirmed intraoperatively in 167 (45.5%) patients. After operation, 175 (47.7%), 83 (22.6%), 32 (8.7%), and 77 (21%) patients were divided into GTR, NTR, STR + ob, and STR + SRS groups, respectively. The mean follow-up time was 40.9 ± 25.8 months. There were 0, 17 (20.5%), 9 (28.1%), and 4 (5.2%) patients noted to have PitNET recurrence or progression in GTR, NTR, STR + ob, and STR + SRS groups, respectively. Event-free survival distribution in the NTR group was similar to that in the STR + ob group (P = .696), which was significantly lower than that in the STR + SRS group (P = .008). Adrenocorticotropic hormone (ACTH)-negative SCAs have lower preoperative ACTH levels and were more likely to invade CS than ACTH-positive SCAs. CS invasion was commonly seen in SCAs, often precluding GTR. Radical surgery and close follow-up were proposed. Early postoperative adjuvant SRS for remnant tumor should be considered.

Adolescent gut microbiome imbalance and its association with immune response in inflammatory bowel diseases and obesity

BackgroundRecently, there has been an increase in the number of studies focusing on the association between the gut microbiome and obesity or inflammatory diseases, especially in adults. However, there is a lack of studies investigating the association between gut microbiome and gastrointestinal (GI) diseases in adolescents.MethodWe obtained 16S rRNA-seq datasets for gut microbiome analysis from 202 adolescents, comprising ulcerative colitis (UC), Crohn’s disease (CD), obesity (Ob), and healthy controls (HC). We utilized Quantitative Insights Into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to acquire Operational Taxonomic Units (OTUs). Subsequently, we analyzed Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology (KO) terms and pathway enrichment for the identified OTUs.ResultsIn this study, we investigated the difference between the gut microbiomes in adolescents with GI diseases and those in healthy adolescents using 202 samples of 16S rRNA sequencing data. The distribution of the six main gut microbiota (i.e., unclassified Dorea, unclassified Lachnospiraceae, unclassified Ruminococcus, Faecalibacterium prausnitzii, Prevotella copri, unclassified Sutterella) was different based on the status of obesity and inflammatory diseases. Dysbiosis was observed within Lachnospiraceae in adolescents with inflammatory diseases (i.e., UC and CD), and in adolescents with obesity within Prevotella and Sutterella. More specifically, our results showed that the relative abundance of Faecalibacterium prausnitzii and unclassified Lachnospiraceae was more than 10% and 8% higher, respectively, in the UC group compared to the CD, Ob, and HC groups. Additionally, the Ob group had over 20% and over 3% higher levels of Prevotella copri and unclassified Sutterella, respectively, compared to the UC, CD, and HC groups. Also, inspecting associations between the six specific microbiota and KO terms, we found that the six microbiota -relating KO terms were associated with NOD-like receptor signaling. These six taxa differences may affect the immune system and inflammatory response by affecting NOD-like receptor signaling in the host during critical adolescence.ConclusionIn this study, we discovered that dysbiosis of the microbial community had varying degrees of influence on the inflammatory and immune response pathways in adolescents with inflammatory diseases and obesity.

Obesity Influences T CD4 Lymphocytes Subsets Profiles in Children and Adolescent's Immune Response

Background:Evidence shows that CD4+ T cells are altered in obesity and play a significant role in the systemic inflammation in adults with the disease. ObjectivesBecause the profile of these cells is poorly understood in the pediatric population, this study aims to investigate the profile of CD4+ T lymphocytes and the plasma levels of cytokines in this population. MethodsUsing flow cytometry, we compared the expression profile of lymphocyte markers, master transcription factors, cytokines, and molecules involved in the regulation of the immune response in CD4+ T cells from children and adolescents with obesity (OB group, n = 20) with those with eutrophy group (EU group, n = 16). Plasma levels of cytokines in both groups were determined by cytometric bead array (CBA). ResultsThe OB group presents a lower frequency of CD3+ T cells, as well as a decreased frequency of CD4+ T cells expressing CD28, IL-4, and FOXP3, but an increased frequency of CD4+IL-17A+ cells compared with the EU group. The frequency of CD28 is increased in Th2 and Treg cells in the OB group, whereas CTLA-4 is decreased in all subpopulations compared with the EU group. Furthermore, Th2, Th17, and Treg profiles can differentiate the EU and OB groups. IL-10 plasma levels are reduced in the OB group and negatively correlated with adiposity and inflammatory parameters. ConclusionsCD4+ T cells have an altered pattern of expression in children and adolescents with obesity, contributing to the inflammatory state and clinical characteristics of these patients.

Impaired exercise-induced increase in serum IGF-1 in humans with obesity

Changes in circulating insulin-like growth factor 1 (IGF-1) implicate regulation of skeletal muscle metabolism, including protein and glucose metabolism. Previous studies have shown that an acute bout of exercise increases serum IGF-1 concentrations in healthy, lean humans. However, exercise-induced changes in serum IGF-1 concentrations in humans with obesity remain unknown. We compared changes in plasma IGF-1 during and after an acute bout of endurance exercise between humans with and without obesity. Eight subjects with obesity (i.e., OB: BMI = 34.48 ± 2.96) and eight subjects without obesity (i.e., LN: BMI = 24.45 ± 2.43 kg/m2) exercised for 45 min in a cycle ergometer at 65% of their maximum oxygen uptake, after an overnight 10-h fast. Blood draws were taken immediately before exercise, at 15 and 30 minutes (i.e., during exercise), and at 55, 75, 95, and 115 minutes after the start of the exercise. Serum concentrations of total IGF-1 and insulin were determined using commercially available ELISA assays (Alpco 22-IGFHU-E01 and 80-INSHU-E10.1, respectively). Plasma glucose concentrations were determined using an automatic analyzer (YSI glucose analyzer). One-way repeated measures analyses of variance were carried out to detect significant changes over time within each group. Independent t tests were used to determine group differences at each time point. Alpha level was set at p ≤ 0.05 and data are reported as mean ± SD. There were no significant ( p &gt; 0.05) differences between groups for IGF-1 serum concentrations at baseline (LN = 205.61 ± 40.07 ng/mL, OB = 200.89 ± 80.40 ng/mL) nor during or after exercise. Significant increases from baseline in serum IGF-1 concentrations were detected in the LN group at 15 min (231.30 ± 50.47 ng/mL, p = 0.007) and 30 min (227.94 ± 49.02 ng/mL, p = 0.04) during exercise, followed by significant decreases from baseline at 95 min (189.99 ± 34.73 ng/mL, p = 0.052) and 115 min (196.42 ± 40.39 ng/mL, p = 0.023). No significant ( p &gt; 0.05) differences from baseline were observed in the obese group neither during nor after exercise. Higher serum insulin concentrations were observed in the OB group at baseline (LN = 5.55 ± 2.62 μIU/mL, OB = 11.07 ± 5.76 μIU/mL, p = 0.027) but significant group differences no longer existed ( p &gt; 0.05) during exercise and up to 55 min after exercise; however, insulin concentrations for the OB group were significantly greater than those measured in the LN group at 75 min ( p = 0.028), 95 min ( p = 0.008), and 115 min ( p = 0.007) after exercise. Moreover, a significant increase from baseline was measured 55 min after exercise in the lean group (8.22 ± 3.13 μIU/mL, p = 0.005), whereas no significant changes were observed in the OB groups at any time point ( p &gt; 0.05). No significant ( p &gt; 0.05) group differences were detected for plasma glucose concentrations at any time point, and despite a significant decrease from baseline observed in the LN group at 115 min after exercise (baseline = 83.32 ± 7.66 mg/dL, 115 min = 81.02 ± 7.00 mg/dL, p = 0.044). In conclusion, endurance exercise increases serum IGF-1 concentrations in humans without obesity, but this response is impaired in humans with obesity. National Institute of Health (NIH)\National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Grant/Award Number: R01DK123441. 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.

Metabolic Recovery with the Persistence of Proinflammatory Leucocyte Dysfunction After Bariatric Intervention for Obesity.

A suitable option for severe obesity treatment is a surgical approach. After surgery, metabolic markers and weight frequently return to adequate values; however, concerning systemic inflammatory mediators, the results are inconsistent. Furthermore, it has been suggested that leucocyte function may be affected even after weight normalization. This study aimed to determine if the surgical treatment of obesity influences the production of cytokines by LPS-stimulated as a function of leucocytes. We performed a cross-sectional study that investigated the production of cytokines in response to lipopolysaccharide (LPS) along a kinetic of simulation by leucocytes recovered from individuals with normal weight (NW, n = 8), persons living with obesity (Ob, n = 7), persons living with obesity and diabetes mellitus (Ob-DM, n = 17), and persons that used to live with obesity who underwent bypass surgery (fOb + bypass, n = 8) and recover normal weigh. IL-6 levels were significantly higher in the Ob and fOb + bypass groups than in NW (p = 0.043). IL-10 secretion without LPS was significantly higher in the NW group than in the other groups explored (p < 0.05). When exposed to LPS, the IL-10 levels increased in all groups except the NW group. As also observed for IL-18 and IL-33, the secretion curve of the fOb + bypass group was more similar to the Ob group, even when they had reached normal weight, as opposed to the NW group. Our results show that in patients with fOb + bypass, inflammatory and anti-inflammatory cytokine production dynamics remain disrupted even with improved metabolic control and normal weight recovery.

Obesity-dependent molecular alterations in fatal COVID-19: A retrospective postmortem study of metabolomic profile of adipose tissue.

We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI],26.5 ± 2.3 kg m-2) or obese (OBBMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OBgroup showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.

Variation in Episiotomy Use Among Nulliparous Individuals by Maternity Care Provider and Associated Rates of Obstetric Anal Sphincter Injury

ObjectivesTo quantify variation in the association between episiotomy and obstetric anal sphincter injury (OASI) by maternity care provider in spontaneous and operative vaginal deliveries (SVDs and OVDs). MethodsPopulation-based retrospective cohort study of vaginal, term deliveries among nullipara in Canada (2004–2015). Adjusted rate ratios (ARRs) and 95% CIs were estimated using log-binomial regression to quantify the associations between episiotomy and OASI, stratified by care provider (obstetrician [OB], family physician [FP], or registered midwife [RM]) while adjusting for potential confounders. ResultsThe study included 631 642 deliveries. Episiotomy use varied by provider: among SVDs, the episiotomy rate was 19.6%, 14.4%, and 8.4% in the OB, FP, and RM groups, respectively. The rate of OASI was higher among SVDs with versus without episiotomy (5.8% vs 4.6%). Conversely, OASI occurred less frequently in operative vaginal deliveries with episiotomy (15.3%) compared with those without (16.7%). In all provider groups, the ARR for OASI was increased with episiotomy in SVD and decreased with episiotomy with forceps delivery. No differences in these associations were observed by provider except among vacuum delivery (ARR with episiotomy vs. without, OB: 0.88, 95% CI 0.84–0.92; FP: 0.89, 95% CI 0.83–0.96, RM: 1.22, 95% CI 1.02–1.48). ConclusionsIn nullipara, irrespective of maternity care provider, there is a positive association between episiotomy and OASI among SVDs and an inverse association between episiotomy and deliveries with forceps. The relationship between episiotomy and OASI is modified by maternity care providers among vacuum deliveries.

GRP78 protein metabolism in obese and diabetic rats: a study of its role in metabolic disorders

ObjectiveThis study aimed to compare and analyze the expression and significance of the GRP78 protein in cochlear cell injury induced by a high glucose and high-fat diet in obese and diabetic rats.MethodsMale SD rats were randomly divided into two groups: normal (NC) and high-fat (HF) groups. The NC group was fed a standard diet for eight weeks, while the HF group received a high-glucose, high-fat diet. The HF group was further categorized into the obesity group (OB group) and the type II diabetes mellitus group (T2DM group). To induce a type II diabetes mellitus (T2DM) model, the T2DM group received an intraperitoneal injection of a small dose of STZ (45 mg/kg). After four weeks on the original diet, body weight, blood glucose, blood lipid levels, and auditory brainstem response (ABR) thresholds were measured. The cochlea was dissected, and its morphology was observed using HE staining. Immunohistochemistry and western blotting were utilized to examine the expression level of the GRP78 protein in the cochlea.Results(1) The ABR threshold demonstrated a statistically significant difference between the T2DM group and the OB group (P < 0.05), as well as between the OB group and the NC group (P < 0.05). (2) Based on morphological comparisons from HE-stained sections, the T2DM group exhibited the most significant alterations in the number of cells in the spiral ganglion, the organ of Corti, and the stria vascularis of the cochlea. (3) The expression level of the GRP78 protein in the cochlea was higher in the T2DM group compared to the OB group (P < 0.05) and higher in the OB group compared to the NC group (P < 0.05).ConclusionThe findings indicate that the GRP78 protein plays a role in hearing loss caused by T2DM and hyperlipidemia. Moreover, T2DM is more likely than hyperlipidemia to be associated with hearing impairment.

Arterial stiffness assessment in obese black South African patients.

Increased arterial stiffness is a determinant of cardiovascular mortality and an independent marker of cardiovascular disease. The objective of this study was to asses arterial elasticity by determination of pulse-wave velocity (PWV) and augmentation index (Aix) in obese black patients. PWV and Aix were assessed non-invasively using the AtCor SphygmoCor® system (AtCor Medical, Inc, Sydney, Australia). The study participants were divided into four groups; healthy volunteers (HV) (n = 29), patients with concomitant diseases but normal body mass index (Nd) (n = 23), obese patients without concomitant diseases (OB) (n = 29) and obese patients with concomitant diseases (OBd) ( n = 29). The difference in the mean levels of PWV was statistically significant in the obese group with and without concomitant disease. The PWV in the OB group (7.9 ± 2.9 m/s) and in the OBd group (9.2 ± 4.4 m/s) was, respectively, 19.7 and 33.3% higher than in the HV group (6.6 ± 2.1 m/s). PWV was directly correlated with age, glycated haemoglobin level, aortic systolic blood pressure and heart rate. The risk of cardiovascular diseases in the obese patient without additional diseases was increased by 50.7%. The presence of concomitant diseases (type 2 diabetes mellitus and hypertension) in addition to obesity increased arterial stiffness by a further 11.4% and therefore also increased the risk of cardiovascular diseases by a further 35.1%. Aix was increased in the OBd and Nd groups by 8.2 and 16.5%, respectively, however the increase was not statistically significant. Aix was directly correlated with age, heart rate and aortic systolic blood pressure. The obese black patients had a higher PWV, indicating increase in arterial stiffness and therefore a higher risk for cardiovascular disease. In addition, aging, increased blood pressure and type 2 diabetes mellitus contributed further to arterial stiffening in these obese patients.

The influence of serum selenium in differential epigenetic and transcriptional regulation of CPT1B gene in women with obesity

IntroductionThe increasing prevalence of obesity has become a major health problem worldwide. The causes of obesity are multifactorial and could be influenced by dietary patterns and genetic factors. Obesity has been associated with a decrease in micronutrient intake and consequently decreased blood concentrations. Selenium is an essential micronutrient for human health, and its metabolism could be affected by obesity, especially severe obesity. This study aimed to identify differential methylation genes associated with serum selenium concentration in women with and without obesity. MethodologyThirty-four patients were enrolled in the study and divided into two groups: Obese (Ob) n = 20 and Non-Obese (NOb) n = 14, according to the Body Mass Index (BMI). Anthropometry, body composition, serum selenium, selenium intake, and biochemical parameters were evaluated. DNA extraction and bisulfite conversion were performed to hybridize the samples on the 450k Methylation Chip Infinium Beadchip (Illumina). Bioinformatics analysis was performed using the R program and the Champ package. The differentially methylated regions (DMRs) were identified using the Bumphunter method. In addition, logarithmic conversion was performed for the analysis of serum selenium and methylation. ResultsIn the Ob group, the body weight, BMI, fat mass, and free fat mass were higher than in the NOb group, as expected. Interestingly, the serum selenium was lower in the Ob than in the NOb group without differences in selenium intake. One DMR corresponding to the CPT1B gene, involved in lipid oxidation, was related to selenium levels. This region was hypermethylated in the Ob group, indicating that the intersection between selenium deficiency and hypermethylation could influence the expression of the CPT1B gene. The transcriptional analysis confirmed the lower expression of the CPT1B gene in the Ob group. ConclusionStudies connecting epigenetics to environmental factors could offer insights into the mechanisms involving the expression of genes related to obesity and its comorbidities. Here we demonstrated that the mineral selenium might play an essential role in lipid oxidation via epigenetic and transcriptional regulation of the CPT1B gene in obesity.

Sex-dependent impact of obesity on aggressiveness of papillary thyroid cancer.

To investigate the impact of body mass index (BMI) on the aggressiveness of papillary thyroid cancer (PTC). A total of 1720 PTC patients with total thyroidectomy or lobectomy, from January 2017 to April 2020, were retrospectively evaluated. Based on BMI, they were divided into two groups, as follows: control (CON, < 24 kg/m2) and overweight and obesity (OB, ≥ 24 kg/m2), each sex being analyzed separately. In the whole cohort, the OB group had significantly higher rates of extrathyroidal extension (21.5 vs. 16.8%, p = 0.013), multifocality (43.2 vs. 37.7%, p = 0.018), and BRAF-V600E mutation (82.9 vs. 79.3%, p = 0.015) than the CON group. In males, the OB group had increased rates of tumor size over 1cm (54.4 vs. 42.7%, p = 0.008), extrathyroidal extension (24.9 vs. 12.4%, p = 0.001), and multifocality (42.7 vs. 33.5%, p = 0.038). The OB group had significantly higher adjusted odds ratios (ORs) of 1.63 (1.14-2.33, p = 0.008), 2.12 (1.26-3.57, p = 0.005), and 1.56 (1.07-2.29, p = 0.022) for tumor size over 1cm, extrathyroidal extension, and multifocality compared with CON. Additionally, overweight and obesity were analyzed alone and the rates of extrathyroidal extension (30/100, 30.0%, p = 0.001) and tumor size over 1cm (65/100, 65.0%, p = 0.001) were significantly higher in the obesity group than in the overweight and CON groups. The obesity group had robust higher adjusted ORs of 2.51(1.50-4.20, p < 0.001), 2.93 (1.50-5.73, p = 0.002) and 1.89 (1.11-3.22, p = 0.020) for tumor size over 1cm, extrathyroidal extension, and multifocality compared with CON. Overweight and obesity were predominant independent risk factors for PTC aggressiveness in males. These data indicated that the therapeutic treatment should be based on risk stratification by BMI in males.

The Yucatan minipig model: A new preclinical model of malnutrition in obese patients with acute or chronic diseases

Background & aimsMalnutrition can develop in patients with obesity suffering from acute or chronic illness or after obesity surgery, promoting sarcopenic obesity. A better understanding of this pathophysiology and the development of new therapeutics for chronic diseases, that are often complicated with malnutrition and obesity, justify the development of new animal experimental models close to the human physiology. This study aims to characterize the effects of obesity and underfeeding on Yucatan obese minipigs, assessing its validity as a preclinical model for obesity-related malnutrition. MethodsSixteen 30-month-old Yucatan minipigs were divided into two groups for 8 weeks: a standard diet group (ST, n=5) and an obesogenic diet group (OB, n=11). After 8 weeks, the OB group was further divided into two sub-groups: a standard diet group (OB-ST, n=5) and a low-calorie/low-protein diet group (OB-LC/LP, n=6) for 8 weeks. Body composition by CT-Scan and blood parameters were monitored, and trapezius muscle biopsies were collected to analyse signaling pathways involved in protein turnover and energy metabolism. ResultsAt W8, OB-ST animals exhibited significantly higher body weight (+37.7%, p=0.03), muscle mass (+24.9%, p=0.02), and visceral fat (+192.0%, p=0.03) compared to ST. Trapezius cross sectional area (CSA) normalized to body weight was lower in OB-ST animals (-15.02%, p=0.017). At W16, no significant changes were observed in protein turnover markers, although REDD1 increased in OB-ST (96.4%, p=0.02). After 8 weeks of low-caloric/low protein diet, OB-LC/LP showed decreased body weight (-9.8%, p=0.03), muscle mass (-6.5%, p=0.03), and visceral fat (-41.5%, p=0.03) compared to OB-ST animals. Trapezius fiber CSA significantly decreased in OB-LC/LP (-36.1%, p<0.0001) and normalized to body weight (-25.4%, p<0.0001), combined to higher ubiquitinated protein content (+38.3%, p=0.02). ConclusionOur data support that the Yucatan minipig model mimics nutritional and skeletal muscle phenotypes observed in obese patients, with or without protein-energy malnutrition. It also reproduces muscle atrophy observed in chronic diseases or post-obesity surgery, making it a promising preclinical model for obesity-related malnutrition.

CD8+ Treg cells play a role in the obesity-associated insulin resistance

Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4+ Treg cells. However, little is known about the CD8+ Treg cells. Therefore, we aim to characterize the CD8+ Treg cells in human peripheral blood and adipose tissue, specifically, to address the effect of obesity and insulin resistance in this regulatory immune cell population. A group of 42 participants with obesity (OB group) were recruited. Fourteen of them were evaluated pre- and post-bariatric surgery. A group of age- and sex-matched healthy volunteers (n = 12) was also recruited (nOB group). CD8+ Treg cell quantification and phenotype were evaluated by flow cytometry, in peripheral blood (PB), subcutaneous (SAT), and visceral adipose tissues (VAT). The OB group displayed a higher percentage of CD8+ Treg cells in PB, compared to the nOB. In addition, they were preferentially polarized into Tc1- and Tc1/17-like CD8+ Treg cells, compared to nOB. Moreover, SAT displayed the highest content of CD8+ Tregs infiltrated, compared to PB or VAT, while CD8+ Tregs infiltrating VAT displayed a higher percentage of cells with Tc1-like phenotype. Participants with pre-diabetes displayed a reduced percentage of TIM-3+CD8+ Tregs in circulation, and PD-1+CD8+ Tregs infiltrated in the VAT. An increase in the percentage of circulating Tc1-like CD8+ Treg cells expressing PD-1 was observed post-surgery.In conclusion, obesity induces significant alterations in CD8+ Treg cells, affecting their percentage and phenotype, as well as the expression of important immune regulatory molecules.

Short stem hip arthroplasty with the optimys prosthesis is a safe and effective option for obese patients: a mid-term follow-up multicenter study

IntroductionShort stems are a valuable option in young patients undergoing total hip arthroplasty (THA) because of their bone stock preserving properties facilitating revision hip arthroplasty. Although the effect of obesity on conventional THA is well studied, data about short stem THA in obese patients are lacking. Therefore, this study aimed to investigate the influence of obesity on complications, revisions, and outcome after short stem THA.Materials and methodsThis multicenter, observational cohort study included patients undergoing short stem THA with the optimys prosthesis. Follow-up examinations were performed at specific intervals up to 7 years postoperatively. Operation characteristics, general and specific complications, revisions, VAS rest pain, VAS load pain, VAS patient satisfaction, and Harris Hip Score (HHS) were recorded and statistically compared between obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) patients.ResultsOf the 224 patients included with a mean follow-up of 87.2 months (range 81.9–104.0), 69 were assigned to the OB group and 155 to the non-OB group. A minimally invasive approach was significantly less often selected in obese patients (p = 0.049), whereas operating time and length of hospital stay were not significantly different. The rate of general and specific complications did not significantly differ between both groups. Survival of the optimys prosthesis was 99.1% at 7-year follow-up and one patient per group had to undergo revision surgery. VAS rest pain, load pain, and satisfaction improved from preoperatively to postoperatively in both groups without a significant difference between both groups. While the HHS was improved from preoperatively to postoperatively, obese patients showed a significantly lower HHS at the 7-year follow-up (p = 0.01) but still exhibited an excellent scoring above the PASS threshold.ConclusionShort stem THA with the optimys prosthesis is a safe and effective option also in obese patients with an excellent clinical outcome and a low complication rate.

The protective effect of N-acetylcysteine on hippocampal ferroptosis in an experimental obesity model

Ferroptosis is a non-apoptotic cell death closely related to a metabolic pathway involving iron overload, imbalanced glutathione metabolism, oxidative stress and lipid peroxidation damage. Obesity is closely associated with these imbalances. In this study, we aimed to investigate the effect of hippocampal ferroptosis in an obesity model and the potential role of N-acetylcysteine (NAC) against ferroptosis. A high-fat (60%) dietary pattern was used to establish an obesity model for 15 weeks. NAC was administered to NAC and Obese+NAC (ObNAC) groups by oral gavage at a dose of 150 mg/kg for 3 weeks. Glutathione peroxidase 4 (GPX4) and the cystine transporter solute carrier family 7- member 11 (SLC7A11) expression levels were investigated immunohistochemically to detect ferroptosis in hippocampal tissues. In the statistical analysis, H-scores of GPX4 and SLC7A11 in the hippocampus sections of the Ob group were significantly lower than in the control, NAC and ObNAC groups (p

Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin.

Background: Obesity and type 2 diabetes mellitus (T2DM) are characterized by underlying low-grade chronic inflammation. Metformin has been used as the first line of therapy in T2DM as it decreases hepatic glucose production and glucose intestinal absorption, enhances insulin sensitivity and weight loss, and is known to ameliorate inflammation. The mechanisms through which metformin exerts its effect remain unclear. Proteomics has emerged as a unique approach to explore the biological changes associated with diseases, including T2DM. It provides insight into the circulating biomarkers/mediators which could be utilized for disease screening, diagnosis, and prognosis. Methods: This study evaluated the proteomic changes in obese (Ob), obese diabetics (OD), and obese diabetic patients on metformin (ODM) using a 2D DIGE MALDI-TOF mass spectrometric approach. Results: Significant changes in sixteen plasma proteins (15 up and 1 down, ANOVA, p ≤ 0.05; fold change ≥ 1.5) were observed in the ODM group when compared to the Ob and OD groups. Bioinformatic network pathway analysis revealed that the majority of these altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. Conclusions: Our study provides important information about the possible biomarkers altered by metformin treatment in obese patients with and without T2DM. These altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. The presented proteomic profiling approach may help in identifying potential biomarkers/mediators affected by metformin treatment in T2DM and inform the understanding of metformin's mechanisms of action.