ABSTRACT Objective To identify heritable factors that affect BMI among Indigenous Americans, we previously conducted a genome‐wide association study using 7.9 million imputed genetic variants from 6789 participants. This study sought to identify a mechanistic link between variants with the strongest association with BMI and adipocyte metabolism. Methods Variants with the strongest association with BMI (rs114857151, rs187498396, and rs189879565; r 2 = 0.99, 2.7% increase in BMI per risk allele, p = 4 × 10 −7 , adjusted for age, sex, birth year, and the first five genetic principal components) were functionally analyzed using luciferase assays. Results These variants map to CYP26B1 , which encodes an enzyme involved in retinoic acid (RA) metabolism. In vitro studies showed that the haplotype with the three risk (higher BMI) variants had a 23% decrease in CYP26B1 transcript variant 3 (TV3) promoter activity. RA response element reporter assays showed that the Cyp26b1 TV3 isoform might be important for RA homeostasis in adipocytes. Cyp26b1 TV3 knockdown in mouse OP9 adipocytes resulted in increased Aldh1a1 expression. Conclusion Alleles carrying these three variants may have reduced expression of CYP26B1 TV3 which in turn influences RA signaling and adipocyte metabolism, providing a possible mechanistic link between CYP26B1 variation and BMI.
ABSTRACT Objective Neurocognitive traits can drive obesity‐related eating behaviors. The orbitofrontal cortex (OFC) integrates reward and sensory information to guide food‐related decision‐making. Here, we build on prior data in individuals without obesity demonstrating that transcranial direct current stimulation (tDCS) of the OFC improves cognitive impulse control to test the effect of OFC tDCS in individuals with obesity. Methods We use a single‐blind, randomized, sham‐controlled study among 60 adults with obesity to test whether either active ( n = 30) or sham ( n = 30) anodal tDCS targeting the left OFC specifically improves cognitive control using the Food and Word‐Color Stroop tasks, the Iowa Gambling Task, and the Stop Signal Task. Results Across all cognitive outcomes, active stimulation did not differ from sham. However, moderation analyses revealed that higher baseline food addiction symptoms were associated with poorer performance with tDCS on the high‐calorie Food Stroop condition, whereas lower impulsivity, lower emotional eating, and higher cognitive restraint were associated with improved post‐stimulation performance on the low‐calorie Food Stroop condition. Conclusions Unlike what has been reported in lean individuals, a single session of OFC‐targeted tDCS is insufficient to modify cognitive control in individuals with obesity. However, the cognitive effects of a single session of OFC stimulation depend on individual neurocognitive characteristics in obesity. Trial Registration ClinicalTrials.gov NCT04218383
OBJECTIVE Despite the high prevalence of obesity and cardiometabolic diseases in safety-net populations, access to intensive, evidence-based lifestyle interventions and scalable implementation strategies remains limited. This study evaluated the effectiveness, acceptability, and feasibility of an interdisciplinary program in an urban safety-net health system. METHODS This single-center, mixed-methods implementation evaluation assessed LA VIDA, a 6-month interdisciplinary weight management program for medically complex individuals. Outcomes included feasibility, patient engagement, self-rated health, quality of life, physical activity, dietary behaviors, and program satisfaction. RESULTS Over 2 years, 95 participants completed the program. They were predominantly female (72.6%) and Latino (78.9%), with a mean age of 50 years, median BMI of 39.2 (IQR: 36.9 to 43.7), and 60% having ≥ 3 comorbidities. Median 6-month weight loss was 5.5% (IQR: -2.6% to -9.9%), with significant improvements in quality of life (p = 0.0003), physical health (p < 0.0001), moderate-intensity physical activity (p < 0.001), and dietary behaviors. Participants reported high satisfaction driven by personalized guidance, increased health knowledge, mindfulness, and the supportive group environment. CONCLUSIONS LA VIDA was feasible and acceptable and improved patient-reported behaviors and outcomes in a safety-net setting. These findings support it as an effective model for integrated obesity care that combines lifestyle, behavioral, and pharmacologic treatment in the safety net.
ABSTRACT Objective Obesity is a major health challenge associated with multiple chronic diseases. Korean traditional medicine (KM) offers diverse therapeutic approaches for obesity management. This study aims to update the Korean Medicine Clinical Practice Guidelines (KMCPGs) by incorporating recent evidence to improve the effectiveness of KM‐based obesity care. Methods The KMCPGs were updated through systematic searches of eight databases for studies published up to December 31, 2022. Evidence quality and recommendation strength were evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results The updated KMCPGs present 20 clinical recommendations, including 7 for KM monotherapies and 13 for KM combination therapies. The recommendations include herbal medicine (A/high), individualized ephedra‐containing prescriptions (GPP), acupuncture (B/low), auricular acupuncture (C/low), electroacupuncture (B/low), pharmacopuncture (B/moderate), TEA (C/low), and 13 combination therapies ranging from grade B to C or GPP. Most recommendations focus on anthropometric outcomes, including body weight, BMI, WC, and body fat‐related measures. Conclusions The update of the KMCPGs underscores the clinical value of KM interventions in obesity management while emphasizing the need for further high‐quality studies to strengthen the evidence. Addressing implementation barriers and ensuring regular guideline updates are essential for optimizing clinical application and improving patient outcomes in obesity care.
