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Roux-en-Y gastric bypass (RYGB) is an effective surgical intervention for severe obesity, but the role of gastrointestinal hormones in its benefits remains unclear. We examined longitudinal pre-to-post-meal gastrointestinal hormone changes and their relationships with glucose homeostasis and feeding-related cognitive responses in women undergoing RYGB. Seventeen non-diabetic women were evaluated pre-RYGB (Visit 1, V1), 1-month post-RYGB (Visit 2, V2), and 1-year post-RYGB (Visit 3, V3). Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), ghrelin, and liver-expressed antimicrobial peptide 2 (LEAP2) were measured before and after a breakfast in all visits. Appetite ratings and feeding-related cognitive performance were evaluated using visual analog scales, Ideal Portion Size, and Food Stroop tasks. At V3, RYGB induced weight loss (30.8%) and improved glucose homeostasis (p = .020), accompanied by reduced hunger (p = .042), smaller self-reported ideal portion size (p < .001), and improved cognitive control toward food-cues (p = .002). Fasting GLP-1 and PYY levels remained stable across visits but showed enhanced post-meal responses at V2 and V3 (GLP-1: p < .001; PYY: p = .013). Ghrelin levels increased post-RYGB (p = .010) without post-meal variation. LEAP2 concentrations remained stable. Fasting LEAP2 correlated positively with BMI at V1 (p < .001). Fasting PYY correlated inversely with BMI at V3 (p = .005), and its post-meal rise inversely correlated with ideal portion size at V1 (p = .022). GLP-1 increments negatively correlated with ideal portion size (p = .007) at all visits and glycemia (p = .017) at V1. In non-diabetic women, RYGB improves feeding-related cognitive processes. BMI is associated with LEAP2 only pre-surgery, and with PYY 1-year post-RYGB. Restoration of GLP-1 and PYY post-meal increments contributes to metabolic and behavioral improvements. Clinical Trial Registry: This study was registered at clinicaltrials.gov as NCT01815216. https://clinicaltrials.gov/study/NCT01815216.

Introduction Roux-en-Y Gastric Bypass (RYGB) is a common treatment option for obesity. After RYGB, loss of both adipose tissue and lean body mass is seen. In this study, we have investigated the dynamic metabolic changes of hyaluronan (HA) and associated biomarkers reflecting the extracellular matrix after RYGB. Materials and Methods In this exploratory cohort study, a total of 306 serum samples were collected at 5 different times from 96 RYGB patients, preoperatively until 6 months after surgery, where 44/96 (46%) contributed samples at 6 months. HA and the cell-surface receptor CD44 were studied by enzyme-linked immunosorbent assay (ELISA), while Luminex Multiplex assays were used for MMP-2, MMP-9, TNF-alpha, IL-1 beta, IL-6 and IL-10. Results Preoperatively, an elevated HA-concentration (> 120 ng/ml) was seen in 39.6% of the study population. From baseline to day of surgery, we found a statistically significant decrease (p < 0.05) in HA (Delta-21.4ng/mL [-42.6, -0.27]), CD44 (Delta-26.7ng/mL [-46.4, -6.9]), MMP-2 (Delta-32.4 ng/mL [-41.4 -23.4]) and MMP-9 (Delta-138.2 ng/mL [-188.0, -88.4]), TNF-alpha(Delta-3.1 pg/mL [-5.4, -0.8]), IL-1 beta (Delta-14.4 pg/mL [-22.2, -6.6]) and IL-6 (Delta-2.0 pg/mL [-3.1, -0.9]). At one month postoperatively, a subsequent increase was seen. Although the mean concentration of HA was unchanged at 6 months, patients with baseline HA >= 120 ng/mL demonstrated a decrease, (Delta-37.1 [-55.8 to -14.7] p < 0.01; exploratory analysis) Conclusion Although mean HA levels returned to baseline at 6 months, a significant transient decrease was observed immediately postoperatively, and patients with elevated preoperative HA (> 120ng/ml) showed a sustained reduction. The postoperative increase of MMP-2 suggests a continuous remodeling of the extracellular matrix.

Background: Metabolic and bariatric surgery (MBS) can be challenging in patients with a very high body mass index (BMI). Objectives: The objective of the study is to evaluate the outcomes of different weight categories in a publicly funded healthcare system with high adherence to current guidelines for perioperative optimization. Setting: Nationwide, registry-based. Methods: Based on nationwide data from the Scandinavian Obesity Surgery Registry, patients operated on with Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and biliopancreatic diversion with duodenal switch (BPD/DS) from 2007 until 2024 were included. Patients were stratified according to preoperative BMIs of 35-49 kg/m2, 50-59 kg/m2, 60-69 kg/m2, and >= 70 kg/m2. Results: The study included data for 83,057 patients. A postoperative complication occurred for 5855 (7.2%) with no difference between BMI groups. Operation time was longer for higher BMI groups for all procedures. At 2 years, patients lost the highest percentage of their total weight (%TWL) in all BMI categories after BPD/DS (37.9% +/- 10.1% to 45.4% +/- 15.3%), followed by RYGB (32.4% +/- 8.6% to 36.8% +/- 10.9%) and SG (26.6% +/- 9.5% to 31.3% +/- 8.9%). Mortality rates over a median of 9.8 years remained higher in the higher BMI groups (BMI: 50-59, odds ratio [OR] = 1.29 [1.15-1.46]; BMI: 60-69, OR = 1.66 [1.18-2.33]; BMI >= 70, OR = 2.33 [.96-5.68]). Conclusion: MBS can be performed safely in patients with obesity class 4 or higher. Higher BMI was associated with longer operating times and superior weight loss, especially after BPD/DS. Despite greater weight loss and similar remission of metabolic co-morbid diseases, patients with higher preoperative BMI still have an increased long-term risk of all-cause mortality. (Surg Obes Relat Dis 2026;22:707-716.) (c) 2026 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Introduction: Physical activity is an important part of accomplishing and maintaining weight loss. As far as the improvement in associated disease is concerned, the effects of Metabolic Bariatric Surgery (MBS) are well known, but the effects on physical activity and ability to perform everyday activities are less obvious. This study explores how weight loss after Roux-en-Y gastric bypass (RYGB) improves physical activity and movement, and how this impacts everyday life.

Method: Semi-structured interviews were held with patients 1-3 years after RYGB. Audio recordings were transcribed verbatim, and the texts were condensed in steps and abstracted with an inductive approach using Qualitative Content Analysis.

Results: 15 individuals, 12 women and 3 men, median age 36 years (26-73), and median body mass index (BMI) 28 (range 22-45), were interviewed until information power was reached. The overall theme "New Life and Freedom" was the result of the analysis process. This was derived from two sub-themes: 1. Discovery of Having Higher Physical Capacity, including the categories Higher Capacity for Physical Activity, No More Limitations, Daily Tasks Are Less Strenuous, and Bodily Change is an Achievement; and 2. Physical Activity is More Rewarding, including the categories Increased Motivation and Initiative, Increased Social Participation, Better Wellbeing, and More Energy.

Conclusion: After MBS, patients describe they have gained a new life and freedom thanks to greater ease of participating in physical activities. Patients should be encouraged to continue increased physical activity during follow-up.

Background

Obesity and Type 2 diabetes (T2D) impair health-related quality of life (HRQoL) across metabolic, mechanical and mental domains. Gastric bypass surgery improves HRQoL in the short term, but long-term trajectories remain insufficiently understood. This study evaluated HRQoL 8 years after gastric bypass in a cohort with T2D, integrating quantitative assessments with qualitative exploration of lived experiences.

Methods

Eleven individuals with obesity and T2D who underwent gastric bypass participated in an 8-year follow-up. Anthropometric and clinical data were collected. HRQoL was assessed using the RAND SF-36, and changes over time were analyzed using repeated-measures ANOVA. Correlations between changes in BMI, HbA1c and HRQoL domains were assessed with Spearman correlations. Semi-structured qualitative interviews were conducted, transcribed verbatim and analyzed using reflexive thematic analysis.

Results

Participants experienced modest weight regain but significant deterioration in glucose control from the 2-year to the 8-year follow-up. RAND SF-36 scores returned to preoperative levels, and the mental health score was significantly reduced compared to the 2-year follow-up (q < 0.01). Weight regain correlated with reduced physical functioning, role-physical and vitality scores (all r < −0.7, p < 0.05), while HbA1c increase correlated with poorer mental health and role-emotional scores (all r < −0.6, p < 0.05). Qualitative interviews revealed that long-term HRQoL was dynamic and shaped by an interplay of physical functioning, psychological wellbeing, body adaptations, social support and life events. An overarching theme emerged: Quality of life after gastric bypass is a multidimensional, evolving process influenced by changing health, life circumstances and psychosocial factors over time.

Conclusions

Initial postoperative improvements in HRQoL were not sustained at 8 years and might have been influenced by weight regain, T2D relapse and intercurrent illness. However, lived experiences highlighted meaningful and durable benefits in physical functioning and self-perception for several participants. The findings underscore the need for long-term, holistic follow-up that integrates metabolic monitoring with psychological and social support.

Trial Registration

ClinicalTrials.gov registration: NCT02729246

FK506-binding protein 51 (FKBP51, encoded by the FKBP5 gene) is a key regulator of glucocorticoid signaling and has been implicated in metabolism and insulin sensitivity, but its specific role in human adipose tissue remains unclear. This study investigated the role of FKBP51 in human adipose tissue and its impact on glucose metabolism and insulin signaling. FKBP5 was measured in paired subcutaneous (SAT) and omental (OAT) adipose tissue samples from 56 subjects with and without obesity, and in SAT from individuals with obesity during weight loss up to 104 weeks post-bariatric surgery. Furthermore, FKBP51 knockdown adipocytes were used to study its effects on insulin signaling and glucose uptake. FKBP5 gene expression, but not protein expression, was significantly lower in obese individuals in both SAT and OAT compared to lean and overweight subjects, and it inversely correlated with insulin resistance measured by homeostatic model assessment of insulin resistance (HOMA-IR). After bariatric surgery, FKBP5 expression in SAT increased to levels similar to those in non-obese controls. Knockdown of FKBP5 in human adipocytes reduced GLUT1 gene expression and insulin-stimulated AKT Ser473 phosphorylation, however, maximal insulin-stimulated glucose uptake rate remained unchanged. Our findings suggest that FKBP5 levels in adipose tissue are reduced in obesity, and this decrease impairs insulin signaling in adipocytes without altering maximal glucose capacity, indicating a limited effect on glucose uptake under the tested conditions.

Studying the pathogenesis of human-adapted microorganisms is challenging, since small animal models often fail to recapitulate human physiology. Hence, the comprehensive genetic and regulatory circuits driving the infection process of principal human pathogens such as Shigella flexneri remain to be defined. We combined large-scale Shigella infections of enteroids and colonoids with transposon-directed insertion sequencing and Bayesian statistical modeling to address infection bottlenecks, thereby establishing the comprehensive genome-wide map of Shigella genes required to infect human intestinal epithelium. This revealed the Shigella virulence effectors essential for epithelial cell colonization across geometries and intestinal segments, identified over 100 chromosomal genes involved in the process and uncovered a post-transcriptional mechanism whereby tRNA-modification enzymes and differential codon usage exert global control of a bacterial virulence program. Our findings provide a broadly applicable framework for combining advanced organotypic tissue culture with functional genomics and computational tools to map human–microorganism interactions at scale.

While obesity and type 2 diabetes (T2D) are associated with altered dopaminergic activity in the central nervous system and in adipose tissue (AT), the directions and underlying mechanisms remain inconclusive. Therefore, we characterized changes in the abundance of dopamine, its metabolites, and receptors DRD1 and DRD2 in the brain and AT upon dietary intervention or obesity. Male Wistar rats were fed either a standard pellet diet, a cafeteria diet inducing obesity and insulin resistance, or a calorie-restricted diet for 12 weeks. Abundance of dopamine and its receptors DRD1 and DRD2 were examined in brain regions relevant for feeding behavior and energy homeostasis. Furthermore, DRD1 and DRD2 protein levels were analyzed in rat inguinal and epidydimal AT and in human subcutaneous and omental AT from individuals with or without obesity. Rats with diet-induced obesity displayed higher dopamine levels, as well as DRD1 or DRD2 receptor levels in the caudate putamen and the nucleus accumbens core. Surprisingly, caloric restriction induced similar changes in DRD1 and DRD2, but not in dopamine levels, in the brain. Both diets reduced DRD1 abundance in inguinal and epidydimal AT, but upregulated DRD2 levels in inguinal AT. Furthermore, in human obesity, DRD1 protein levels were elevated only in omental AT, while DRD2 was upregulated in both omental and subcutaneous AT. These findings highlight dopaminergic responses to changes in energy balance, occurring both in the brain and AT. We propose that dopaminergic pathways are involved in tissue crosstalk during the development of obesity and T2D.

Context

Obesity and insulin resistance in men are linked to decreased testosterone and increased estradiol (E2) levels. Aromatase (ARO) converts testosterone into E2, and this occurs mainly in adipose tissue in men. E2 acts through estrogen receptors ESR1 and ESR2, and they potentially affect development of type 2 diabetes (T2D).

Objective

This study explored alterations in ARO, ESR1, and ESR2 in men with obesity or T2D.

Methods

Subcutaneous adipose tissue (SAT) from men with or without obesity or T2D was analyzed for ARO, ESR1, and ESR2 gene and protein expression. Data were compared across groups and correlated with markers of obesity, glycemia, insulin resistance, and sex hormones. Moreover, SAT was incubated with E2 or testosterone for ex vivo glucose uptake measurements.

Results

ARO levels were higher in SAT from men with obesity compared to nonobese men, and gene expression correlated positively with adiposity, hyperglycemia, and insulin resistance. No association was found between ARO and circulating E2. Men with obesity had lower levels of ESR1 and ESR1:ESR2 ratio, but not ESR2. ESR1 gene expression in SAT correlated negatively with adiposity and insulin resistance markers as well as with ARO expression, and tended to be lower in men with T2D. E2 reduced insulin-stimulated glucose uptake, while testosterone increased basal glucose uptake in adipocytes.

Conclusion

Elevated ARO in SAT was found in obese men, and this was linked to insulin resistance and glycemia, supporting the idea that local estrogen production contributes to metabolic dysregulation. ESR1 was reduced in men with T2D and was linked to adiposity and insulin resistance. Taken together, high ARO and altered ESR1:ESR2 balance in SAT in obese men may contribute to insulin resistance and T2D development.