Obesity (Silver Spring, Md.)最新文献

Objective: White adipose tissue (WAT) expansion occurs through generation of new adipocytes from adipose progenitor cells (APC). The objective of this study was to characterize and validate a new transcriptional profile of APC.

Methods: Single-cell (sc)/nuclei (sn) RNA-Seq was performed on nuclei from whole WAT (n = 20), cells from WAT stromal vascular fraction (n = 5), and cultured APC in vitro (n = 8) using ICELL8 smart-Seq technology. Additional snRNA-Seq was performed on WAT using 10x genomic platform. Pseudotime analyses and differentiation of hiPSCs was used to track the temporal patterns of novel gene signatures. Immunohistochemistry was performed to validate a new marker.

Results: A pre-adipocyte population was found across the four independent datasets that expressed known pre-adipocyte markers (ZNF423 and DLK1) in addition to genes typically associated with neurogenes (DPP10, PTRPT, CTNNA2, NRXN3, CTNNA2, PTPRD, CNTNAP2 and RBFOX1). The expression of these genes were temporally regulated with adipocyte differentiation. Immunohistochemistry analyses confirmed these pre-adipocytes are located in the neurovascular niche of WAT but are not neurons or endothelial cells.

Conclusions: This work has defined a new transcriptional signature of pre-adipocytes in human subcutaneuous WAT that are distinct from mesencyhmal stem cell populations and represent novel targets for WAT expansion.

Objective: This study aimed to investigate the association between SGLT2 inhibitor (dapagliflozin) use in patients with type 2 diabetes (T2D) and changes in body weight and liver fat.

Methods: This is a secondary analysis of a randomized placebo-controlled trial. Fifty-six patients with T2D were randomized to placebo or 10 mg dapagliflozin. Anthropometrics, liver MRI-proton density fat fraction (PDFF), fasting glucose, HbA1c, and liver function tests were measured at baseline and at 12 months. The relationship between dapagliflozin use and changes in body weight and liver fat was investigated using multiple linear regression models and mediation analysis.

Results: In this cohort, 76% of participants had hepatic steatosis. Groups were similar in cardiometabolic risk factors and in liver fat fraction values. Compared to placebo, dapagliflozin resulted in reduction in liver MRI-PDFF (-3.7% vs. 0.5%, p = 0.001), body weight (-3.84 vs. -1.42 kg, p = 0.015), and HbA1c (-0.52 vs. 0.11, p = 0.012). Mediation analysis confirmed the direct effect of the SGLT2 inhibitor on change in liver fat and showed that the indirect effect of weight loss on change in liver fat was not statistically significant.

Conclusions: Twelve months of dapagliflozin was associated with a significant reduction in liver fat as measured by MRI-PDFF compared to placebo; this effect was independent of weight loss and other known beneficial metabolic effects of SGLT2 inhibition.

Trial registration: ClinicalTrials.gov: NCT03782259.

Objective: This prespecified subpopulation analysis aimed to assess the efficacy and safety of once-weekly tirzepatide versus placebo alongside lifestyle intervention in Japanese adults with obesity or overweight.

Methods: Data from 102 Japanese adults in the SURMOUNT-1 trial with BMI ≥ 30 kg/m² or ≥ 27 kg/m² and ≥ 1 weight-related comorbidity were analyzed. Coprimary endpoints were mean percent change in body weight and the proportion of participants who achieved ≥ 5% body weight reduction at week 72.

Results: Participants in the tirzepatide 5-, 10-, and 15-mg groups had a statistically significantly greater (all p < 0.001) least squares mean (standard error) percent change in body weight compared with those in the placebo group: -12.0% (1.7%), -22.4% (1.7%), -22.1% (1.6%), and -0.3% (1.6%), respectively. Overall, 91.7%, 100%, and 96.6% of participants in the tirzepatide 5-, 10-, and 15-mg groups, respectively, had ≥ 5% weight reduction at week 72, compared with 15.4% in the placebo group. Significant improvements in cardiometabolic measures were also observed with tirzepatide at week 72 compared to placebo. No new safety concerns were identified.

Conclusions: Once-weekly treatment with tirzepatide demonstrated significant reductions in body weight and prespecified cardiometabolic measures compared with placebo in Japanese adults with obesity or overweight.

Trial registration: ClinicalTrials.gov identifier: NCT04184622 https://clinicaltrials.gov/study/NCT04184622.

Objective: This study aimed to describe real-world obesity medication (OM) prescribing and dispensing among adolescents and young adults (AYAs) and examine factors associated with dispensing.

Methods: A retrospective cohort linked Nemours Children's Health electronic health record (EHR) to Surescripts dispensing (2020-2025). AYAs aged 12-20 with prescriptions for liraglutide, semaglutide, phentermine, phentermine-topiramate, or tirzepatide were included; youth with diabetes were excluded. Primary outcome was ever dispensed. Multilevel logistic regression assessed the odds of dispensing by race and ethnicity, Child Opportunity Index (COI), health insurance, prescription (Rx) coverage, drug, and prescription year.

Results: Among 1194 AYAs with ≥ 1 OM prescription, 56.7% received ≥ 1 fill. Versus semaglutide, dispensing odds were higher for liraglutide (OR 2.40), phentermine (OR 3.32), and phentermine-topiramate (OR 2.16) and lower for tirzepatide (OR 0.45; all p ≤ 0.003). Hispanic AYAs had lower odds than non-Hispanic White peers (OR 0.61; p ≤ 0.001). Public (OR 1.31) and mixed insurance (OR 1.63) and Rx coverage (OR 2.00; all p ≤ 0.05) were associated with higher odds. Despite increased rates of prescribing each year, rates of dispensing declined.

Conclusions: Nearly half of AYA OM prescriptions were never dispensed. Barriers to initiation persist and inequities affect Hispanic youth. Addressing insurance/Rx coverage constraints may improve equitable access.

Objective: Preoperative weight changes, predictors of weight changes, and subsequent implications on postoperative BMI reduction in adolescents preparing for bariatric surgery (MBS) have not been well described.

Methods: Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) consortium (prospective, observational MBS study at five centers from 2007 to 2011) participants who completed the preoperative phase within 3-9 months of initial visit were included in this analysis (n = 123). Participants were categorized into preoperative weight groups: > 1% loss, stable, or > 1% gain. Demographic, anthropometric, socioeconomic, medical, and behavioral data were analyzed. Postoperative percent BMI loss at 1, 5, and 8 years by weight group was compared.

Results: Preoperatively, 50% of participants lost weight, 20% remained stable, and 30% gained weight. The mean percent weight change by group was -4.2% (standard deviation [SD] 2.9%), +0.02% (SD 0.6%), and +5.2% (SD 5.3%), respectively. Eight-year postoperative BMI change was -21% (lost) and -26% (stable), compared to -15% among those who gained weight preoperatively (p = 0.11). No differences in preoperative weight-related behaviors were observed between groups.

Conclusions: Most adolescents preparing for MBS maintained ±5% of their baseline weight. No statistically significant differences in postoperative BMI loss or factors predicting preoperative weight change were identified.

Trial registration: ClinicalTrials.gov identifier: NCT00474318.

Objective: Obesity is an imperfect correlate of metabolic health. Visceral adipose tissue (VAT) characteristics are considered determinants of poor health and subcutaneous adipose tissue (SAT) considered protective. There is a gap in knowledge regarding shared vs. unique SAT and VAT function across the metabolic syndrome (MetS) spectrum.

Methods: We quantified SAT and VAT transcriptomes in a nonhuman primate model of MetS. We calculated quantitative MetS risk scores using composite factors, applied unbiased clustering methods (weighted gene correlation network analysis) to identify transcripts that correlated with MetS risk scores, and performed pathway enrichment analysis.

Results: We found convergence in SAT and VAT on T-cell signaling genes and pathways, with T-cell exhaustion signaling prominent. Pathways unique to VAT highlighted interferon signaling and innate/adaptive immune cross talk in response to pathogens. Pathways unique to SAT included innate immune cell signaling, centered on vascular involvement. Although molecular signatures highlight T-cell signaling, T-cell abundance in VAT was unrelated to MetS scores.

Conclusions: T-cell signaling and exhaustion predominate in metabolically unhealthy adaptations of both SAT and VAT. This novel handling of transcript data using an unbiased clustering approach and the creation of continuous MetS scores lead to new insights regarding adipose depot responses and T-cell biology.

Objective: This study assessed whether changes in body composition or fat distribution after weight loss are associated with cardiometabolic improvements, independent of weight loss magnitude.

Methods: We analyzed data from a 1-year lifestyle intervention in adults with obesity and type 2 diabetes (Study I) and a 12-week hypocaloric diet intervention in adults with overweight/obesity without diabetes (Study II). Body composition was assessed by DXA and fat distribution by either abdominal computed tomography (Study I) or DXA-derived trunk to total fat ratio (Study II). Insulin sensitivity was assessed by glucose clamp (Study I) and HOMA-IR (both studies). Additional markers included glucose, lipids, and blood pressure. Changes in body composition and fat distribution were adjusted for baseline values and weight loss using regression analysis.

Results: Body weight decreased by 9.8% in Study I and 5.3% in Study II, with fat mass accounting for 64% (95% CI: 0.51%-0.77%) and 77% (95% CI: 0.68%-0.86%) of weight lost, respectively. Clamp-derived insulin sensitivity increased by 50% (Study I), and HOMA-IR decreased by 26% in both studies. No cardiometabolic changes were associated with weight loss-adjusted changes in body fat percentage or fat distribution.

Conclusions: Cardiometabolic improvements from weight loss appear independent of changes in body fat percentage or fat distribution.

Objective: The huge obesity prevalence and related metabolic disorders highlight the urgent need for new therapeutic strategies beyond lifestyle interventions. Despite the availability of novel pharmacological treatments, the search for more effective and safe antiobesity compounds remains a challenge. Recent advances in high-performance computational drug discovery have enabled the rapid screening and identification of potential antiobesity compounds [Correction added on 10 February 2026, after first online publication: "Methods" was deleted from this sentence.]. However, these in silico procedures frequently require complex computational knowledge that limits the use of these techniques for most researchers and hampers interdisciplinary works.

Methods: To address this gap, we have developed OBE-DB, an accessible and user-friendly platform integrating computational tools that facilitates the prediction of potential antiobesity molecules through two complementary approaches: (i) shape similarity analysis against a curated database of approved obesity drugs and (ii) inverse virtual screening of user-submitted molecules against a set of therapeutic protein targets linked to obesity.

Results: Our results demonstrate that the server effectively screens and ranks compounds with high predicted activity, outperforming conventional in silico techniques in terms of accuracy and usability.

Conclusion: The OBE-DB web server represents a significant advancement by providing researchers with an intuitive tool to accelerate early-stage drug discovery for obesity treatment. The server is freely accessible without registration, providing users with a detailed report via email upon completion of the predictions. This innovative database and web server is accessible online via https://bio-hpc.ucam.edu/obe-db/.

Objective: This cross-sectional study examined associations between sleep, body weight, body composition, appetite, and food reward after bariatric surgery.

Methods: A single 7-day study period in 22 female adults (age, 53.5 ± 9.3 years; BMI, 35.5 ± 8.5 kg/m²; body fat: 44.9% ± 8.6%) who underwent bariatric surgery ≥ 1 year prior to enrollment assessed: actigraphy-measured sleep (duration, efficiency, midpoint, and variability [coefficient of variation]) and activity energy expenditure (AEE); sleep architecture and apnea-hypopnea index (AHI) via in-home polysomnography; energy intake via food diaries; resting EE via indirect calorimetry; fasting appetite via visual analog scales; and food reward via Leeds Food Preference Questionnaire.

Results: Weight regain was 10.6% relative to nadir postsurgery weight. Rapid eye movement (REM) sleep duration was associated with lower body fat percentage (r = -0.52, p = 0.02). Participants with AHI ≥ 5 had a greater waist to hip ratio compared to those with AHI < 5 (mean difference = 0.09, p = 0.01). Sleep timing and duration variability was associated with fasting prospective food consumption (r = 0.44, p = 0.05 and r = 0.47, p = 0.03, respectively). Greater sleep duration was associated with lower AEE (r = -0.62, p < 0.01) and explicit liking for sweet foods (r = 0.45, p = 0.04).

Conclusions: Our exploratory results underscore the need to evaluate whether sleep behaviors, including total and REM sleep duration, AHI, and sleep regularity, predict long-term weight loss maintenance after bariatric surgery.

Objective: This study compared the effects of phentermine-topiramate-ER (mid-dose 7.5/46 mg) versus placebo on weight loss and cardiovascular disease (CVD) risk outcomes when used as an adjunct to a digitally enhanced lifestyle intervention (DELI).

Methods: We conducted a 12-month, randomized, double-blind, placebo-controlled trial at a single tertiary academic center in the United States (June 2020-June 2022). Eighty participants with obesity (BMI ≥ 30 kg/m²) were enrolled in the DELI program, consisting of in-person and telehealth modalities, dietary and physical activity goals, and use of a smartphone application integrated with digital devices (Apple Watch and Bluetooth-enabled weight scale and blood pressure monitor). Participants were randomized 1:1 to receive either phentermine-topiramate-ER (n = 42) or placebo (n = 38) in addition to the DELI.

Results: At 3 months, the phentermine-topiramate group lost a mean of 10.82 kg versus 4.04 kg in the placebo group (mean difference -6.78 kg; p = 0.002). At 12 months, weight loss was 15.32 kg versus 5.85 kg, respectively (mean difference -9.48 kg; p < 0.001). Participants receiving phentermine-topiramate-ER experienced a 3.35% reduction in the estimated atherosclerotic CVD risk compared to baseline (p = 0.004).

Conclusions: Phentermine-topiramate-ER, when combined with a DELI, produced significant and sustained weight loss and reduced CVD risk in adults with obesity.

Trial registration: ClinicalTrials.gov: NCT04408586.