BURA Collection:

Severe obesity as an oligogenic condition: evidence from 1714 adults seeking treatment in the UK National Health Service

2026-09-09T02:08:40Z

Title: Severe obesity as an oligogenic condition: evidence from 1714 adults seeking treatment in the UK National Health Service Authors: Almansoori, Sumaya; Amin, Hasnat A; Alsters, Suzanne I; Handley, Dale; Yiorkas, Andrianos M; Hashim, Nikman Adli Nor; Ramzi, Nurul Hanis; Bonanomi, Gianluca; Small, Peter; Purkayastha, Sanjay; van Haelst, Mieke; Walters, Robin G; le Roux, Carel W; Chahal, Harvinder S; Drenos, Fotios; Blakemore, Alexandra IF Abstract: Previous evidence has established genetics as an important contributing factor to severe (class III) obesity, which is a chronic, relapsing condition, with a high burden of comorbidity and mortality. We therefore designed a custom genotyping array to screen a cohort of UK patients seeking treatment for severe obesity in a cost-effective way. A total of 1,714 participants were genotyped using a custom AXIOM array, focusing on rare (minor allele frequency < 0.01) variants, with CADD-PHRED ≥ 15 in 78 genes known/suspected to cause Mendelian forms of obesity. Concordance analyses of 22 duplicate samples and 66 samples with whole exome sequence data revealed good genotyping reliability. We identified the proportion of study participants who carried, or were homozygous for, rare, predicted-deleterious variants in genes with dominant and recessive modes of inheritance (MOI), respectively. 27% of patients carried relevant mutations consistent with the expected MOI, which was very similar to the rate observed in the UKB 50 K whole exome sequencing dataset. However, the clinical obesity cohort was more likely to carry two or more such variants, in separate genes, than UK Biobank participants (17.1% vs. 13%, p = 0 0.018), which strongly indicates the possibility of oligogenic inheritance. In conclusion, our results provide evidence: that (i) custom genotyping arrays, used with improved algorithms can allow reliable, cost-effective screening for rare genetic variants; (ii) rare mutations in “obesity genes” may be at high prevalence among bariatric patients, as well as in the general population; and (iii) that severe obesity may have an oligogenic pattern of inheritance in some cases. Description: Data availability: Data is provided within the manuscript or supplementary information files. Also additional data supporting the finding of this study are available upon request from the corresponding author.; Supplementary Information is available online at: https://link.springer.com/article/10.1186/s40246-025-00895-7#Sec20 .

Rapid and long-lasting remodelling of the blood transcriptome following bariatric surgery

2026-09-09T02:08:37Z

Title: Rapid and long-lasting remodelling of the blood transcriptome following bariatric surgery Authors: Roux, Julien; Seyres, Denis; Buxton, Jessica L; Handley, Dale; Hofer, Giulia; Alsters, Suzanne I; Herzig, Karl-Heinz; Järvelin, Marjo-Riitta; Blakemore, Alexandra I; Cavelti-Weder, Claudia Abstract: Background/Objectives: Bariatric (or metabolic) surgery is the most effective treatment for severe obesity, resulting in sustained weight loss and rapid improvement in metabolic outcomes. However, it is currently unknown what molecular changes are induced by the surgery, how they relate to the health improvements, how early they occur, and whether they are maintained over time. Subjects/Methods: In this study, we characterised early gene expression changes following surgery in blood samples from the ‘Personalised Medicine for Morbid Obesity’ cohort. Results: We observed widespread changes in gene expression only a few days after surgery. Pathways related to immune response were affected, in particular with a decreased expression of the NF-κB pathway and neutrophil cytotoxic activity genes, suggesting a reduction of the inflammatory state typically associated with obesity. Metabolic signalling was also affected, with decreased expression of genes from pathways related to glucagon and insulin secretion, and key regulators such as the appetite-controlling hormone ghrelin. Comparisons to publicly available transcriptomics datasets showed that beyond these specific changes, bariatric surgery induces a transcriptome-wide reversal of expression changes associated with obesity and with forms of type 2 diabetes related to obesity. Comparisons to transcriptomics studies with longer-term follow-ups after bariatric surgery showed that a large fraction of early-induced expression changes likely persist for several months. Conclusions: Taken together, we show that previously unreported early changes in blood gene expression after bariatric surgery provide in-depth insights into the resolution of the chronic inflammation associated with severe obesity and its connection with metabolic improvement. Description: Data availability: Processed data (read count table) are available from GEO, under accession GSE273902. Raw data are not available due to patient privacy concerns.

Disruption of the thyroid hormone system and patterns of altered thyroid hormone serum concentrations after chemical exposures in adult rodents – a systematic review

2026-09-28T09:36:38Z

Title: Disruption of the thyroid hormone system and patterns of altered thyroid hormone serum concentrations after chemical exposures in adult rodents – a systematic review Authors: Baig, Asma H; Forner-Piquer, Isabel; Ermler, Sibylle; Kortenkamp, Andreas Abstract: Identification of thyroid hormone system-disrupting chemicals (THSDC) requires a solid understanding of the mechanisms by which exposure leads to adverse outcomes in the thyroid hormone system (THS). In this systematic review we present the results from our extensive evidence mapping of thyroid hormone (TH) and thyroid stimulating hormone (TSH) patterns in serum or plasma, after exposure to various THSDCs in adult rodents. Our review of 234 peer-reviewed studies revealed that only a small group of compounds induced changes in T4 and TSH consistent with the canonical view of the hypothalamic-pituitary-thyroid (HPT) negative feedback loop, whilst the most frequent pattern was a decrease in T4 without TSH changes. The lack of a TSH response may have been due to T4 decreases not being sufficient to change HPT feedback. However, risk-of-bias analysis also identified deficits in TH/TSH analytical methodology, including the timepoints of TH measurements, possibly explaining discrepancies between studies. We further compared T4/TSH patterns to mechanism-of-action information and other THS-related outcomes and found that THSDC frequently affected TH synthesis, induced hepatic enzymes involved in TH metabolism, and exhibited other differences in pharmacokinetic properties. Given the diverse chemical nature of the various THSDCs and variety of molecular targets in the THS, there is likely no single explanation for the different patterns observed. Our compilation of T4/TSH patterns observed after different chemical exposures demonstrated that it is important to not solely rely on the canonical serum hormonal patterns to determine adversity of chemical exposures. Chemicals with different responses should be carefully considered, as current regulatory criteria may fail to identify them as being harmful to human health. Description: Data availability statement: The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.; Supplementary material: The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fendo.2026.1911254/full#supplementary-material

Hydrogels Augmented With Artificial Sweeteners can Inhibit Multidrug‐Resistant Acinetobacter baumannii Growth and Biofilm Formation While Demonstrating Safety in Pre‐Clinical Pilot Human Trials

2026-08-28T02:01:35Z

Title: Hydrogels Augmented With Artificial Sweeteners can Inhibit Multidrug‐Resistant Acinetobacter baumannii Growth and Biofilm Formation While Demonstrating Safety in Pre‐Clinical Pilot Human Trials Authors: Han, Jie; Soliman, Mohamed; Zhang, Bin; Krawiel, Dominika; McCarthy, Ronan R Abstract: There is a critical need for novel therapeutic strategies to tackle multidrug‐resistant bacterial infections. Artificial sweeteners (AS) specifically acesulfame potassium, sodium saccharin, and sodium cyclamate, have recently demonstrated antimicrobial activity against multidrug‐resistant bacteria. In this study, polyvinyl alcohol (PVA)‐borate hydrogel is developed as a carrier for antimicrobial AS to combat wound infections. Through extensive optimization, we developed cytocompatible 8% AS‐loaded hydrogels with 3% PVA + 3% borax that reduced the viability of multidrug‐resistant Acinetobacter baumannii AB5075 by 99.9% colony‐forming unit enumeration following 1 h hydrogel treatment. Most currently available wound dressings have limited efficacy against bacterial biofilms, but we demonstrate that each of these sweeteners can attenuate A. baumannii and Pseudomonas aeruginosa dual‐microbial biofilms. Haemolysis and cell viability assays demonstrate excellent blood compatibility and non‐cytotoxic behavior of the sweetener‐loaded hydrogels. To further evaluate the clinical potential of these AS‐loaded hydrogels, we conducted a pilot Phase I clinical study with human volunteers focused on evaluating short‐term safety and irritancy. This study revealed that the dressings had no adverse effects on the volunteers. This research underscores the translational potential of hydrogels augmented with AS and their capacity to overcome many of the hurdles that typically lead to wound dressing failure. Description: Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.